ClinVar Miner

Submissions for variant NM_001148.6(ANK2):c.7412G>A (p.Ser2471Asn)

gnomAD frequency: 0.00006  dbSNP: rs375139170
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001056431 SCV001220874 uncertain significance Long QT syndrome 2022-09-27 criteria provided, single submitter clinical testing In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The asparagine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. ClinVar contains an entry for this variant (Variation ID: 851921). This variant has not been reported in the literature in individuals affected with ANK2-related conditions. This variant is present in population databases (rs375139170, gnomAD 0.02%). This sequence change replaces serine, which is neutral and polar, with asparagine, which is neutral and polar, at codon 2471 of the ANK2 protein (p.Ser2471Asn).
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001811634 SCV001474411 uncertain significance not provided 2020-08-23 criteria provided, single submitter clinical testing The ANK2 c.7412G>A, p.Ser2471Asn variant (rs375139170), to our knowledge, is not reported in the medical literature but is reported as uncertain in ClinVar (Variation ID: 851921). This variant is found in the African population with an allele frequency of 0.02% (2/24,958 alleles) in the Genome Aggregation Database. The serine at codon 2471 is moderately conserved, and computational analyses (SIFT: tolerated, PolyPhen-2: possibly damaging) predict conflicting effects of this variant on protein structure/function. Due to limited information, the clinical significance of the p.Ser2471Asn variant is uncertain at this time. Gene statement: Pathogenic variants in ANK2 are associated with autosomal dominant ankyrin-B-related cardiac arrhythmia and long QT syndrome 4 (MIM: 600919).
Ambry Genetics RCV002379569 SCV002671265 likely benign Cardiovascular phenotype 2020-06-13 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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.
Fulgent Genetics, Fulgent Genetics RCV002482013 SCV002784244 uncertain significance Cardiac arrhythmia, ankyrin-B-related 2021-07-29 criteria provided, single submitter clinical testing

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