ClinVar Miner

Submissions for variant NM_005691.3(ABCC9):c.2199-13G>A (rs201226082)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000214647 SCV000530283 likely benign not specified 2017-11-21 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.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000214647 SCV000271481 uncertain significance not specified 2017-08-10 criteria provided, single submitter clinical testing Variant classified as Uncertain Significance - Favor Benign. The c.2199-13G>A va riant in ABCC9 has been identified in our laboratory in one individual with dila ted cardiomyopathy. It has also been identified in 0.2% (22/10238) of African ch romosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitu te.org; dbSNP rs201226082). This variant has been reported in ClinVar (Variation ID: 228423). Computational tools do not suggest an impact on splicing, though t his information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the c.2199-13G>A variant is uncertain, its fr equency suggests that it is more likely to be benign.
Stanford Center for Inherited Cardiovascular Disease,Stanford University RCV000786076 SCV000924708 uncertain significance not provided 2017-09-05 no assertion criteria provided provider interpretation c.2199-13G>A in intron 16 of the ABCC9 gene (NM_005691.2; 12:22017424C>T) The Laboratory for Molecular Medicine classifies this variant as a variant of uncertain significance. However, they state it is more likely to be benign. Given the absence of case data and its high prevalence in the general population, we consider this variant a variant of uncertain significance, likely benign, and we do not feel it is suitable for assessing risk in healthy relatives ("predictive genetic testing"). The variant has been seen in at least 2 unrelated (unpublished) cases of dilated cardiomyopathy (including this patient's family). The ABCC9 gene is most commonly associated with familial atrial fibrillation, dilated cardiomyopathy and hypertrichotic osteochondrodysplasia (Cantu syndrome). There is no published case data. This variant is present in ClinVar: GeneDx classifies this variant as likely benign. Per the test report, "computational tools do not suggest an impact on splicing, though this information is not predictive enough to rule out pathogenicity." The cytosine in the gDNA at position 2199 is moderately conserved across species. Neighboring nucleic acids are more strongly conserved. There are two other nearby intronic variants close to this one that are both classified as (likely) benign: c.2199-6T>C and c.2199-11T>C. The variant was reported online in 53 of 138,163 individuals in the Genome Aggregation Consortium Dataset (gnomAD; http://gnomad.broadinstitute.org/), which currently includes variant calls on >140,000 unrelated individuals of African, Asian, European, Ashkenazi, Latino descent. Specifically, the variant was observed in 49 of 11,984 individuals of African descent (MAF=0.2%) and 4 of 17,148 individuals of Latino descent. The phenotype of those individuals is not publicly available. The dataset is comprised of multiple cohorts, some of which were recruited from the general population, others were enriched for common cardiovascular disease.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.