ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.376G>A (p.Gly126Ser) (rs779153546)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000198159 SCV000250003 uncertain significance not provided 2018-08-02 criteria provided, single submitter clinical testing The G126S variant in the COL5A2 gene has not been reported previously as a pathogenic variant, nor as a benign variant, to our knowledge. The G126S variant is observed in 8/34402 (0.0233%) alleles from individuals of Latino background, and 15/277018 total alleles in large population cohorts (Lek et al., 2016). The G126S variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. In-silico analyses, including protein predictors and evolutionary conservation, support that this variant does not alter protein structure/function. We interpret G126S as a variant of uncertain significance.
Invitae RCV000634610 SCV000755942 uncertain significance Ehlers-Danlos syndrome, classic type 2018-08-01 criteria provided, single submitter clinical testing This sequence change replaces glycine with serine at codon 126 of the COL5A2 protein (p.Gly126Ser). The glycine residue is highly conserved and there is a small physicochemical difference between glycine and serine. This variant is present in population databases (rs779153546, ExAC 0.009%). This variant has not been reported in the literature in individuals with COL5A2-related disease. ClinVar contains an entry for this variant (Variation ID: 213140). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably 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.

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