ClinVar Miner

Submissions for variant NM_172364.5(CACNA2D4):c.1617G>C (p.Glu539Asp)

gnomAD frequency: 0.00001  dbSNP: rs767999612
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV001114228 SCV001272080 uncertain significance Retinal cone dystrophy 4 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, this variant 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 (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV001856505 SCV002244152 uncertain significance not provided 2022-10-17 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with aspartic acid, which is acidic and polar, at codon 539 of the CACNA2D4 protein (p.Glu539Asp). This variant is present in population databases (rs767999612, gnomAD 0.003%). 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: 883632). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.
Ambry Genetics RCV004032182 SCV004914901 uncertain significance Inborn genetic diseases 2023-12-30 criteria provided, single submitter clinical testing The c.1617G>C (p.E539D) alteration is located in exon 15 (coding exon 15) of the CACNA2D4 gene. This alteration results from a G to C substitution at nucleotide position 1617, causing the glutamic acid (E) at amino acid position 539 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.

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