ClinVar Miner

Submissions for variant NM_172364.5(CACNA2D4):c.1407C>G (p.Tyr469Ter)

dbSNP: rs771184759
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778355 SCV000914570 uncertain significance Retinal cone dystrophy 4 2018-11-12 criteria provided, single submitter clinical testing The CACNA2D4 c.1407C>G (p.Tyr469Ter) variant is a stop-gained variant, predicted to result in premature termination of the protein, which was observed by ICSL 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 for this variant, it could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change. No publications were found based on this search. Due to the potential impact of stop-gained variants and the lack of clarifying evidence, this variant is classified as a variant of unknown significance but suspicious for pathogenicity for retinal cone dystrophy.
Invitae RCV001856157 SCV002125273 uncertain significance not provided 2023-08-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr469*) in the CACNA2D4 gene. It is expected to result in an absent or disrupted protein product. However, the current clinical and genetic evidence is not sufficient to establish whether loss-of-function variants in CACNA2D4 cause disease. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with CACNA2D4-related conditions. ClinVar contains an entry for this variant (Variation ID: 631672). 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.

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