ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.2879C>T (p.Ala960Val)

gnomAD frequency: 0.00003  dbSNP: rs762396014
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000489666 SCV000577147 uncertain significance not provided 2017-04-10 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1A gene. The A961V variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The A961V variant is not observed at a significant frequency in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The A961V variant is a conservative amino acid substitution, which is not likely to impact secondary protein structure as these residues share similar properties. This substitution occurs at a position that is not conserved. In silico analysis is inconsistent in its predictions as to whether or not the variant is damaging to the protein structure/function. Based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV001237622 SCV001410388 likely benign Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2022-09-01 criteria provided, single submitter clinical testing
Neuberg Supratech Reference Laboratories Pvt Ltd, Neuberg Centre for Genomic Medicine RCV001823144 SCV002073160 uncertain significance Developmental and epileptic encephalopathy, 42 criteria provided, single submitter clinical testing The missense variant p.A961V in CACNA1A (NM_001127221.1) has been previusly reported in ClinVar as a variant of uncertain significance. The missense variant c.2882C>T (p.A961V) in CACNA1A (NM_001127221.1) is observed in 1/19310 (0.0052%) alleles from individuals of South Asian background in the gnomAD dataset (Exome Aggregation Consortium et al, 2016), but was not seen in the homozygous state. The p.A961V missense variant is predicted to be tolerated by both SIFT or PolyPhen2. The nucleotide c.2882 in CACNA1A is not conserved according to a GERP++ and PhyloP analysis of 100 vertebrates. For these reasons, this variant has been classified as Uncertain Significance.

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