Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Department Of Translational Genomics |
RCV000171381 | SCV000221578 | uncertain significance | not provided | 2024-02-14 | criteria provided, single submitter | research | reclassified to VUS based on updated frequency (PMID: 31130284) |
| Invitae | RCV001087082 | SCV000627676 | likely benign | Long QT syndrome | 2023-12-11 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001194187 | SCV001363528 | likely benign | not specified | 2023-02-06 | criteria provided, single submitter | clinical testing | Variant summary: ANK2 c.8324A>G (p.His2775Arg) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 7.6e-05 in 249628 control chromosomes, predominantly at a frequency of 0.00093 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 93 fold of the estimated maximal expected allele frequency for a pathogenic variant in ANK2 causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.8324A>G has been reported in the literature in a setting of whole exome sequencing in one individual affected with tachycardia, without strong evidence for causality (Luo_2020). This report does not provide unequivocal conclusions about association of the variant with Arrhythmia. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 and all classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| Gene |
RCV000171381 | SCV001767510 | likely benign | not provided | 2019-11-14 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002426815 | SCV002677134 | likely benign | Cardiovascular phenotype | 2020-12-24 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |