ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.1245A>G (p.Glu415=)

gnomAD frequency: 0.00608  dbSNP: rs34145832
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000231068 SCV000286233 benign Long QT syndrome 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000254172 SCV000320271 benign Cardiovascular phenotype 2015-09-28 criteria provided, single submitter clinical testing This alteration is classified as 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.
Illumina Laboratory Services, Illumina RCV001094944 SCV000447150 benign Cardiac arrhythmia, ankyrin-B-related 2018-01-13 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 benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000780828 SCV000918422 benign not specified 2018-02-05 criteria provided, single submitter clinical testing Variant summary: ANK2 c.1245A>G alters a conserved nucleotide resulting in a synonymous change located in the Ankyrin repeat-containing domain (IPR020683) of the encoded protein sequence. One computational tool predicts the variant creates cryptic exonic 3' acceptor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0018 in 276932 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 184.16 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 benign. To our knowledge, no occurrence of c.1245A>G in individuals affected with Arrhythmia and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
GeneDx RCV001706251 SCV001859859 benign not provided 2015-03-03 criteria provided, single submitter clinical testing
Genome-Nilou Lab RCV001094944 SCV002524995 benign Cardiac arrhythmia, ankyrin-B-related 2021-12-05 criteria provided, single submitter clinical testing
Clinical Genetics, Academic Medical Center RCV000780828 SCV001926138 benign not specified no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV000780828 SCV001955813 benign not specified no assertion criteria provided clinical testing

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