ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.754G>T (p.Gly252Cys) (rs1553517323)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626682 SCV000747385 likely pathogenic Telecanthus; Hyperextensible skin; Joint hypermobility; Spinal deformities 2017-01-01 criteria provided, single submitter clinical testing
Invitae RCV001220827 SCV001392839 likely pathogenic Ehlers-Danlos syndrome, classic type 2019-07-03 criteria provided, single submitter clinical testing This sequence change replaces glycine with cysteine at codon 252 of the COL5A2 protein (p.Gly252Cys). The glycine residue is highly conserved and there is a large physicochemical difference between glycine and cysteine. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be de novo in an individual with clinical features of connective tissue disease (Invitae). ClinVar contains an entry for this variant (Variation ID: 523366). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be disruptive, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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