ClinVar Miner

Submissions for variant NM_001854.4(COL11A1):c.2916+1G>A

dbSNP: rs2101595036
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
3billion RCV002250987 SCV002521289 likely pathogenic Stickler syndrome type 2 2022-05-22 criteria provided, single submitter clinical testing The variant is not observed in the gnomAD v2.1.1 dataset. Canonical splice site: predicted to alter splicing and result in a loss or disruption of normal protein function through nonsense-mediated decay (NMD) or protein truncation. Multiple pathogenic variants are reported downstream of the variant. Therefore, this variant is classified as likely pathogenic according to the recommendation of ACMG/AMP guideline.
Invitae RCV003094077 SCV003271962 pathogenic not provided 2023-11-11 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 38 of the COL11A1 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in COL11A1 are known to be pathogenic (PMID: 20513134, 21035103, 23922384, 25240749, 32427345, 32756486). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individuals with clinical features of autosomal dominant Stickler syndrome (PMID: 10486316). ClinVar contains an entry for this variant (Variation ID: 1687305). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
PreventionGenetics, part of Exact Sciences RCV004533996 SCV004722757 likely pathogenic COL11A1-related disorder 2024-02-14 criteria provided, single submitter clinical testing The COL11A1 c.2916+1G>A variant is predicted to disrupt the GT donor site and interfere with normal splicing. To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Nearby splicing variants (c.2916+1G>T and c.2916+2T>C) were reported in individuals with Marshall/Stickler Phenotype (Annunen. 1999. PubMed ID: 10486316). At PreventionGenetics, this variant was observed in another patient underwent test for Stickler syndrome panel. Variants that disrupt the consensus splice donor site in COL11A1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

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