ClinVar Miner

Submissions for variant NM_020297.4(ABCC9):c.407-14C>A

gnomAD frequency: 0.00248  dbSNP: rs201279882
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Total submissions: 13
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000038615 SCV000062293 likely benign not specified 2012-05-10 criteria provided, single submitter clinical testing c.407-14C>A in intron 3 of ABCC9: This variant is not expected to have clinical significance because it has been identified in 0.5% (32/7020) of European Americ an chromosomes from a broad population by the NHLBI Exome Sequencing Project (ht tp://evs.gs.washington.edu/EVS).
GeneDx RCV000038615 SCV000166783 benign not specified 2014-04-07 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina RCV000312271 SCV000377564 uncertain significance Dilated cardiomyopathy 1O 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina RCV000366987 SCV000377565 likely benign Hypertrichotic osteochondrodysplasia Cantu type 2018-01-12 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000852673 SCV000995380 benign Arrhythmogenic right ventricular cardiomyopathy 2019-03-25 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001530112 SCV001472361 benign not provided 2023-08-24 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038615 SCV001482154 benign not specified 2021-02-15 criteria provided, single submitter clinical testing Variant summary: ABCC9 c.407-14C>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0031 in 250376 control chromosomes, predominantly at a frequency of 0.0048 within the South Asian subpopulation in the gnomAD database. The observed variant frequency within South Asian control individuals in the gnomAD database is approximately 307 fold of the estimated maximal expected allele frequency for a pathogenic variant in ABCC9 causing Dilated Cardiomyopathy phenotype (1.6e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of South Asian origin. c.407-14C>A has been reported in the literature in individuals with dilated cardiomyopathy along with other possible pathogenic/likely pathogenic/uncertain significance variants (Pugh_2014). This reports however, does not provide unequivocal conclusions about association of the variant with Dilated Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as benign.
Labcorp Genetics (formerly Invitae), Labcorp RCV000312271 SCV002397275 benign Dilated cardiomyopathy 1O 2024-01-30 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001530112 SCV001744758 likely benign not provided no assertion criteria provided clinical testing
Clinical Genetics, Academic Medical Center RCV000038615 SCV001919715 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000038615 SCV001931740 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000038615 SCV001956126 benign not specified no assertion criteria provided clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000038615 SCV001968820 benign not specified no assertion criteria provided clinical testing

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