Submissions for variant NM_001844.5(COL2A1):c.156C>A (p.Cys52Ter)

dbSNP: rs1246771678

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659383	SCV000781194	likely pathogenic	Stickler syndrome type 1	2016-11-01	criteria provided, single submitter	clinical testing
Invitae	RCV001387827	SCV001588547	pathogenic	not provided	2020-02-07	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). This variant has not been reported in the literature in individuals with COL2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 547245). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Cys52*) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product.
GeneDx	RCV001387827	SCV004168645	pathogenic	not provided	2023-10-10	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD)
PreventionGenetics, part of Exact Sciences	RCV003938010	SCV004747486	likely pathogenic	COL2A1-related condition	2024-01-26	criteria provided, single submitter	clinical testing	The COL2A1 c.156C>A variant is predicted to result in premature protein termination (p.Cys52*). To our knowledge, this variant has not been reported in the literature or in a large population database, indicating this variant is rare. Nonsense variants in COL2A1 are expected to be pathogenic. This variant is interpreted as likely pathogenic.