ClinVar Miner

Submissions for variant NM_001127222.2(CACNA1A):c.6217G>A (p.Asp2073Asn)

gnomAD frequency: 0.00001  dbSNP: rs1057524336
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000422871 SCV000535247 uncertain significance not provided 2016-12-30 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CACNA1A gene. The D2074N variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The D2074N variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). The D2074N variant is a semi-conservative amino acid substitution, which may impact secondary protein structure as these residues differ in some properties. In silico analysis predicts this variant is probably damaging to the protein structure/function. However, this substitution occurs at a position where amino acids with similar properties to Aspartic acid are tolerated across species. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001340110 SCV001533907 uncertain significance Episodic ataxia type 2; Developmental and epileptic encephalopathy, 42 2022-11-26 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CACNA1A protein function. ClinVar contains an entry for this variant (Variation ID: 392047). This variant has not been reported in the literature in individuals affected with CACNA1A-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change replaces aspartic acid, which is acidic and polar, with asparagine, which is neutral and polar, at codon 2074 of the CACNA1A protein (p.Asp2074Asn).

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