Variant Annotation
Available parameters and response documentation is available here
GET /lookup/7-151945072--T?add-ACMG-annotation=1
{ "chromosome": "chr7", "alt": "T", "ref": "", "pos": 151945072, "variant_id": "10190071519450720005", "regions": { "uniprot_regions": { "version": "04-Oct-2024", "items": [ { "absolute_positon": 2623199191, "amino_acid": "M1-K54,K54-E84,E84-S130,S130-K197,K197-G247,G247-E283,R284-S338,S338-K395,K395-K433,N434-R490,R490-D541,D541-A579,A579-V605,V605-Q844,G845-V884,G885-G923,V924-Q957,D958-K992,I993-W1053,W1053-R1108,R1108-V1145,V1145-D1167,D1167-E1238,E1238-G1281...", "chromo": "chr7", "colour": "255,0,0", "description": null, "length": 301079, "position": 151832010, "protein": "KMT2C_HUMAN", "type": "homo_sapiens proteome sequences", "pub_med_references": null } ] } }, "variant_type": "Insertion", "cytobands": "7q36.1", "refseq_transcripts": [ { "items": [ { "name": "NM_170606.3", "strand": "-", "coding_impact": "nonsense", "function": [ "NMD", "coding" ], "hgvs": "c.2447dup", "hgvs_p1": "Y816*", "hgvs_p3": "p.(Tyr816Ter)", "location": "exon 14 of 59 before position 635 of 719", "coding_location": "816 of 4912", "canonical": true, "gene_symbol": "KMT2C", "splice_distance": "-86", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": "ENST00000262189.11", "mane_plus": null, "uniprot_id": null } ], "version": "224" } ], "ensembl_transcripts": [ { "items": [ { "name": "ENST00000262189.6", "strand": "-", "coding_impact": "nonsense", "function": [ "NMD", "coding" ], "hgvs": "c.2447dup", "hgvs_p1": "Y816*", "hgvs_p3": "p.(Tyr816Ter)", "location": "exon 14 of 59 before position 635 of 719", "coding_location": "816 of 4912", "canonical": true, "gene_symbol": "KMT2C", "splice_distance": "-86", "ensembl_support_level": "1", "ensembl_appris": "principal2", "mane_select": "NM_170606.3", "mane_plus": null, "uniprot_id": "Q8NEZ4" }, { "name": "ENST00000355193.2", "strand": "-", "coding_impact": "nonsense", "function": [ "NMD", "coding" ], "hgvs": "c.2447dup", "hgvs_p1": "Y816*", "hgvs_p3": "p.(Tyr816Ter)", "location": "exon 14 of 60 before position 635 of 719", "coding_location": "816 of 4969", "canonical": false, "gene_symbol": "KMT2C", "splice_distance": "-86", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": "Q8NEZ4" }, { "name": "ENST00000418673.1", "strand": "-", "coding_impact": "nonsense", "function": [ "NMD", "coding" ], "hgvs": "c.32dup", "hgvs_p1": "Y11*", "hgvs_p3": "p.(Tyr11Ter)", "location": "exon 1 of 6 before position 34 of 118", "coding_location": "11 of 227", "canonical": false, "gene_symbol": "KMT2C", "splice_distance": "-86", "ensembl_support_level": "5", "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": null }, { "name": "ENST00000558084.1", "strand": "-", "coding_impact": null, "function": [ "non-coding exon" ], "hgvs": null, "hgvs_p1": null, "hgvs_p3": null, "location": "exon 14 of 59 before position 635 of 719", "coding_location": null, "canonical": false, "gene_symbol": "KMT2C", "splice_distance": "-86", "ensembl_support_level": null, "ensembl_appris": null, "mane_select": null, "mane_plus": null, "uniprot_id": null } ], "version": "112" } ], "gnomad_exomes": [ { "version": "2.1.1", "filter": "InbreedingCoeff;RF", "ac": 81747, "an": 167790, "af": 0.48719828356874667, "ac_afr": 3538, "ac_amr": 11304, "ac_asj": 3268, "ac_eas": 6142, "ac_eas_kor": 1169, "ac_eas_jpn": 59, "ac_eas_oea": 4914, "ac_fin": 7706, "ac_nfe": 38135, "ac_nfe_bgr": 993, "ac_nfe_est": 93, "ac_nfe_nwe": 13432, "ac_nfe_onf": 10619, "ac_nfe_seu": 3882, "ac_nfe_swe": 9116, "ac_oth": 1883, "ac_sas": 9771, "ac_afr_male": 1341, "ac_amr_male": 4636, "ac_asj_male": 1671, "ac_eas_male": 3014, "ac_fin_male": 4014, "ac_nfe_male": 21421, "ac_oth_male": 970, "ac_sas_male": 7438, "ac_afr_female": 2197, "ac_amr_female": 6668, "ac_asj_female": 1597, "ac_eas_female": 3128, "ac_fin_female": 3692, "ac_nfe_female": 16714, "ac_oth_female": 913, "ac_sas_female": 2333, "ac_male": 44505, "ac_female": 37242, "an_afr": 7504, "an_amr": 23102, "an_asj": 6766, "an_eas": 12322, "an_eas_kor": 2350, "an_eas_jpn": 118, "an_eas_oea": 9854, "an_fin": 15734, "an_nfe": 78650, "an_nfe_bgr": 2018, "an_nfe_est": 192, "an_nfe_nwe": 28022, "an_nfe_onf": 21774, "an_nfe_seu": 8030, "an_nfe_swe": 18614, "an_oth": 3936, "an_sas": 19776, "an_afr_male": 2848, "an_amr_male": 9490, "an_asj_male": 3466, "an_eas_male": 6050, "an_fin_male": 8194, "an_nfe_male": 44160, "an_oth_male": 2022, "an_sas_male": 15044, "an_afr_female": 4656, "an_amr_female": 13612, "an_asj_female": 3300, "an_eas_female": 6272, "an_fin_female": 7540, "an_nfe_female": 34490, "an_oth_female": 1914, "an_sas_female": 4732, "an_male": 91274, "an_female": 76516, "age_hist_het_under_30": 1591, "age_hist_het_30_35": 2238, "age_hist_het_35_40": 2966, "age_hist_het_40_45": 5541, "age_hist_het_45_50": 6766, "age_hist_het_50_55": 8176, "age_hist_het_55_60": 7573, "age_hist_het_60_65": 6858, "age_hist_het_65_70": 5847, "age_hist_het_70_75": 3942, "age_hist_het_75_80": 2726, "age_hist_het_over_80": 1319, "variant_type": "mixed", "segdup": true, "original_variant": "7-151945071-G-GT", "main_data": "ƒ = 0.487" } ], "gnomad_exomes_coverage": [ { "version": "2.1", "coverage_mean": [ 99.37200164794922 ], "coverage_median": [ 100.0 ], "coverage_20_frequency": [ 1.0 ] } ], "gnomad_genomes": [ { "version": "2.1.1", "filter": "InbreedingCoeff", "ac": 10703, "an": 22162, "af": 0.4829437776373973, "ac_afr": 2353, "ac_amr": 311, "ac_asj": 98, "ac_eas": 633, "ac_fin": 1243, "ac_nfe": 5677, "ac_nfe_est": 1714, "ac_nfe_nwe": 3153, "ac_nfe_onf": 781, "ac_nfe_seu": 29, "ac_oth": 388, "ac_afr_male": 1372, "ac_amr_male": 152, "ac_asj_male": 70, "ac_eas_male": 424, "ac_fin_male": 591, "ac_nfe_male": 3171, "ac_oth_male": 176, "ac_afr_female": 981, "ac_amr_female": 159, "ac_asj_female": 28, "ac_eas_female": 209, "ac_fin_female": 652, "ac_nfe_female": 2506, "ac_oth_female": 212, "ac_male": 5956, "ac_female": 4747, "an_afr": 4982, "an_amr": 634, "an_asj": 198, "an_eas": 1272, "an_fin": 2564, "an_nfe": 11714, "an_nfe_est": 3496, "an_nfe_nwe": 6530, "an_nfe_onf": 1628, "an_nfe_seu": 60, "an_oth": 798, "an_afr_male": 2914, "an_amr_male": 308, "an_asj_male": 142, "an_eas_male": 852, "an_fin_male": 1216, "an_nfe_male": 6566, "an_oth_male": 368, "an_afr_female": 2068, "an_amr_female": 326, "an_asj_female": 56, "an_eas_female": 420, "an_fin_female": 1348, "an_nfe_female": 5148, "an_oth_female": 430, "an_male": 12366, "an_female": 9796, "age_hist_het_under_30": 1536, "age_hist_het_30_35": 433, "age_hist_het_35_40": 480, "age_hist_het_40_45": 673, "age_hist_het_45_50": 955, "age_hist_het_50_55": 1200, "age_hist_het_55_60": 931, "age_hist_het_60_65": 736, "age_hist_het_65_70": 495, "age_hist_het_70_75": 280, "age_hist_het_75_80": 123, "age_hist_het_over_80": 51, "variant_type": "mixed", "segdup": true, "original_variant": "7-151945071-G-GT", "main_data": "ƒ = 0.483" } ], "gnomad_genomes_coverage": [ { "version": "2.1", "coverage_mean": [ 92.58300018310547 ], "coverage_median": [ 100.0 ], "coverage_20_frequency": [ 1.0 ] } ], "ncbi_clinvar2": [ { "version": "05-Dec-2024", "review_status": "criteria provided, single submitter", "review_stars": 1, "variation_id": 403020, "num_submitters": 2, "pub_med_references": null, "clinical_significance": [ "Benign" ], "last_evaluation": "20240623", "origin": null, "accessions": [ { "variation_id": 403020, "accession_id": "RCV001251811", "review_status": "no assertion criteria provided", "allele_id": 390552, "review_description": "Likely benign", "clinical_significance": [ "Likely benign" ], "date_created": 20200815, "title": "NM_170606.3(KMT2C):c.2447dup (p.Tyr816Ter) AND Intellectual disability", "finding": [ { "normalized_phenotype": [ "Intellectual Disability" ], "symbols": { "medgen": "C3714756", "mesh": "D008607", "mondo": "MONDO:0001071", "human_phenotype_ontology": "HP:0007180" }, "names": [ "Intellectual Disability", "Intellectual Functioning Disability", "Intellectual Disability", "Intellectual Developmental Disorder" ] } ], "review_date": 20190101, "review_stars": 0, "submission_description": [], "variant_id": 10190071519450720005, "submissions": [ { "submitter_date": 20200505, "submission_description": [], "review_description": "Likely benign", "submitter_name": "Centre de Biologie Pathologie Génétique, Centre Hospitalier Universitaire de Lille", "review_date": 20190101, "origin": "inherited", "method": "clinical testing", "finding": [ { "symbols": { "hp": "HP:0001249" }, "normalized_phenotype": [ "Intellectual Disability" ] } ], "date_updated": 20200815, "clinical_significance": [ "Likely benign" ], "review_status": "no assertion criteria provided", "accession_id": "SCV001427553" } ] }, { "variation_id": 403020, "accession_id": "RCV000455198", "review_status": "criteria provided, single submitter", "allele_id": 390552, "review_description": "Benign", "clinical_significance": [ "Benign" ], "date_created": 20170410, "title": "NM_170606.3(KMT2C):c.2447dup (p.Tyr816Ter) AND not specified", "diseases": [ { "symbols": { "medgen": "CN169374" }, "names": [ "Not Specified", "Allhighlypenetrant" ] } ], "review_date": 20160425, "review_stars": 1, "submission_description": [], "variant_id": 10190071519450720005, "submissions": [ { "submitter_date": 20170403, "submission_description": [ "Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: frequency" ], "review_description": "Benign", "submitter_name": "Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine", "review_date": 20160425, "origin": "germline", "method": "clinical testing", "diseases": [ { "names": [ "Not Specified" ] } ], "date_updated": 20170410, "clinical_significance": [ "Benign" ], "review_status": "criteria provided, single submitter", "accession_id": "SCV000539482" } ] } ], "main_data": "benign **1**", "names": [ "NM_170606.3(KMT2C):c.2447dup (p.Tyr816Ter)", "p.Tyr816X" ], "variant_type": "Duplication" } ], "publications": { "publications": [ { "referenced_by": [ "VarSome users" ], "pub_med_id": 26014803 } ], "genes": [ { "publications": [ { "referenced_by": [ "gene2phenotype" ], "pub_med_id": 38146907 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 36360262 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 35685914 }, { "referenced_by": [ "gene2phenotype" ], "pub_med_id": 35324822 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 35108799 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 34958143 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 33619735 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 33482836 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 32366967 }, { "referenced_by": [ "gene2phenotype" ], "pub_med_id": 31712638 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 30847515 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 30564305 }, { "referenced_by": [ "gene2phenotype", "GenCC", "PanelApp" ], "pub_med_id": 29276005 }, { "referenced_by": [ "gene2phenotype", "GenCC", "PanelApp", "CGD", "dbNSFP" ], "pub_med_id": 29069077 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 28263302 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 28191890 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 26185613 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 26167905 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 26166478 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 25989142 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 25363768 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 25326635 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 25294932 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 24581740 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 24267887 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 24090431 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 23999528 }, { "referenced_by": [ "GenCC" ], "pub_med_id": 23375656 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 23042784 }, { "referenced_by": [ "GenCC", "PanelApp", "CGD", "dbNSFP" ], "pub_med_id": 22726846 }, { "referenced_by": [ "PanelApp" ], "pub_med_id": 20212079 }, { "referenced_by": [ "dbNSFP" ], "pub_med_id": 17500065 } ], "gene_symbol": "KMT2C", "gene_id": 12315 } ] }, "publication_counts": [ { "type": "variant", "id": "10190071519450720005", "count": 2 }, { "type": "gene", "id": 12315, "count": 343, "symbol": "KMT2C" } ], "saphetor_known_pathogenicity": [ { "version": "07-Feb-2025", "items": [ { "annotations": { "NCBI ClinVar2": [ { "functions": [ "NMD", "coding" ], "coding_impact": "nonsense", "acmg_confirmed": false, "acmg_class": "Benign", "acmg_reannotated": "Likely Pathogenic", "source": "NCBI ClinVar2", "codon": 816, "gene_symbol": "KMT2C", "hgvs": "Y816*", "transcript": "NM_170606.3", "submission_count": 2, "review_stars": 1, "accession_count": 2, "publication_count": 0, "clinical_significance": [ "benign" ], "disease_name": [ "Allhighlypenetrant", "Intellectual Developmental Disorder", "Intellectual Disability", "Intellectual Functioning Disability", "Not Specified" ] } ], "Saphetor PubMedUserEntry": [ { "functions": [ "NMD", "coding" ], "coding_impact": "nonsense", "acmg_confirmed": false, "acmg_class": "Uncertain Significance", "acmg_reannotated": "Likely Pathogenic", "source": "Saphetor PubMedUserEntry", "codon": 816, "gene_symbol": "KMT2C", "hgvs": "Y816*", "transcript": "NM_170606.3", "pub_med_references": [ 26014803 ], "pathogenicity": "DA", "id": 10096, "confirmedByFunctionalStudy": false } ] } } ] } ], "acmg_annotation": { "version_name": "12.8.2", "gene_symbol": "KMT2C", "transcript": "NM_170606.3", "transcript_reason": "MANE select", "coding_impact": "nonsense", "verdict": { "ACMG_rules": { "benign_score": 1, "benign_subscore": "Likely Benign", "clinical_score": 4.257, "pathogenic_score": 8, "pathogenic_subscore": "Likely Pathogenic", "total_score": 7, "verdict": "Likely Pathogenic" }, "classifications": [ "PVS1", "BP6" ] }, "classifications": [ { "name": "PVS1", "met_criteria": true, "user_explain": [ "Null variant (nonsense) in gene KMT2C, predicted to cause NMD. Loss-of-function is a known mechanism of disease (gene has 143 reported pathogenic LOF variants). The exon contains 5 pathogenic variants. The truncated region contains 140 pathogenic variants." ] }, { "name": "BP6", "met_criteria": true, "user_explain": [ "Combined evidence strength is Supporting (score = 1).", "Supporting: ClinVar classifies this variant as Benign, 1 star (reviewed Jun '24, 2 submissions of which 1 is from high confidence submitter)." ] } ], "gene_id": 12315, "sample_findings": { "phenotypes": "No matching phenotype found for gene KMT2C which is associated with Intellectual Disability, Intellectual Disability, Autosomal Dominant 40, Kleefstra Syndrome 2, Kleefstra Syndrome 2 617768 and 3 more, according to CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp and gene2phenotype.", "mode_of_inheritance": "AD, based on gene information from CGD, ClinGen Disease Validity, GenCC, Mondo, PanelApp and gene2phenotype." } }, "phylop100way": [ { "version": "13-Apr-2021", "conservation_score": [ "0.907", "4.789", "6.663" ] } ], "maxentscan": null }