ClinVar Miner

Submissions for variant NM_000393.5(COL5A2):c.2291C>G (p.Pro764Arg) (rs150260969)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000242357 SCV000319507 benign Cardiovascular phenotype 2017-01-24 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Center for Human Genetics, Inc RCV000680515 SCV000807901 uncertain significance Connective tissue disorder 2018-06-01 criteria provided, single submitter clinical testing
GeneDx RCV000198963 SCV000249969 uncertain significance not specified 2017-04-20 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL5A2 gene. The P764R variant has not been published as pathogenic or been reported as benign to our knowledge. However, it is classified as a variant of uncertain significance in ClinVar by two other clinical laboratories (ClinVar SCV000319507.1, SCV000547891.1; Landrum et al., 2016). The P764R 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. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, this variant has been observed in 58/66,568 (0.09%) alleles from individuals of Non-Finnish European ancestry in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Additionally, this variant does not affect a Glycine residue in a Gly-X-Y motif in the triple helical region of the COL5A2 gene, where the majority of pathogenic missense variants occur (Stenson et al., 2014; Symoens et al., 2012). However, in contrast to several other collagen genes, relatively few pathogenic Glycine substitutions have been reported in COL5A2 in association with Ehlers-Danlos syndrome. Most pathogenic variants in COL5A2 are in-frame splice site changes that cause exon skipping (Symoens et al., 2012).
Illumina Clinical Services Laboratory,Illumina RCV000387034 SCV000425644 likely benign Ehlers-Danlos syndrome, type 7A 2016-06-14 criteria provided, single submitter clinical testing
Invitae RCV000467216 SCV000547891 likely benign Ehlers-Danlos syndrome, classic type 2017-12-09 criteria provided, single submitter clinical testing

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