ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.870+5G>A

dbSNP: rs794727095
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Eurofins Ntd Llc (ga) RCV000174511 SCV000225823 uncertain significance not provided 2016-06-08 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000174511 SCV001211215 uncertain significance not provided 2022-02-03 criteria provided, single submitter clinical testing 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. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 194199). This variant has been observed in individual(s) with clinical features of Stickler syndrome (PMID: 20179744). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 13 of the COL2A1 gene. It does not directly change the encoded amino acid sequence of the COL2A1 protein. It affects a nucleotide within the consensus splice site.
GeneDx RCV000174511 SCV001789814 likely pathogenic not provided 2021-03-05 criteria provided, single submitter clinical testing Reported in ClinVar (ClinVar variant ID# 194199; Landrum et al., 2016); Not observed in large population cohorts (Lek et al., 2016); Damages or destroys the splice donor site in intron 13, and is expected to cause abnormal gene splicing; if the splice outcome is exon skip, the loss of the encoded residues in the triple helical region is expected to disrupt normal protein folding and function, and this is an established mechanism of disease (Stenson et al., 2014); Other splicing variants at the same nucleotide position (c.870+5 G>T) and the same splice donor site (c.870+1 G>A) have been reported in HGMD in association with Stickler syndrome (Stenson et al., 2014); This variant is associated with the following publications: (PMID: 30245029, 20179744, 25525159)
PreventionGenetics, part of Exact Sciences RCV004537369 SCV004739885 uncertain significance COL2A1-related disorder 2023-11-14 no assertion criteria provided clinical testing The COL2A1 c.870+5G>A variant is predicted to interfere with splicing. This variant is predicted to decrease the strength of the canonical splice donor site (Alamut Visual Plus v1.61). This variant was reported in an individual with Stickler syndrome (Hoornaert. 2010. PubMed ID: 20179744) and in a cohort of individuals with hearing loss (c.663+5G>A in Table S3, Azaiez. 2018. PubMed ID: 30245029). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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