ClinVar Miner

Submissions for variant NM_001844.5(COL2A1):c.1957C>T (p.Arg653Ter)

dbSNP: rs121912893
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000481275 SCV000568539 pathogenic not provided 2021-10-22 criteria provided, single submitter clinical testing Reported in multiple individuals with Stickler syndrome referred for genetic testing at GeneDx and in published literature (Wilkin et al., 2000; Liberfarb et al., 2003; Richards et al., 2005; Hoornaert et al., 2010; Richards et al., 2010; Savasta et al., 2015); Estimated to account for 2% of molecularly confirmed cases of Stickler syndrome type 1 (Barat-Houari et al., 2016); Not observed in large population cohorts (gnomAD); 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; Reported in ClinVar as pathogenic (ClinVar Variant ID# 17395; ClinVar); Also known as R453*; This variant is associated with the following publications: (PMID: 20179744, 20301479, 20513134, 16752401, 10982970, 26443184, 12544472, 12939326, 24164106, 25809783, 29453956, 15671297, 26747767)
Fulgent Genetics, Fulgent Genetics RCV000762896 SCV000893296 pathogenic Achondrogenesis type II; Avascular necrosis of femoral head, primary, 1; Multiple epiphyseal dysplasia, Beighton type; Legg-Calve-Perthes disease; Kniest dysplasia; Namaqualand hip dysplasia; Spondyloperipheral dysplasia; Stickler syndrome type 1; Platyspondylic dysplasia, Torrance type; Spondylometaphyseal dysplasia; Spondyloepiphyseal dysplasia congenita; Spondyloepiphyseal dysplasia with metatarsal shortening; Stickler syndrome, type I, nonsyndromic ocular; Spondyloepiphyseal dysplasia, Stanescu type 2018-10-31 criteria provided, single submitter clinical testing
Blueprint Genetics RCV000481275 SCV001832299 pathogenic not provided 2019-11-30 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000481275 SCV002126178 pathogenic not provided 2024-11-21 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg653*) in the COL2A1 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in COL2A1 are known to be pathogenic (PMID: 20179744). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individuals with Stickler syndrome (PMID: 12544472). This variant is also known as p.R453X. ClinVar contains an entry for this variant (Variation ID: 17395). For these reasons, this variant has been classified as Pathogenic.
Greenwood Genetic Center Diagnostic Laboratories, Greenwood Genetic Center RCV000018938 SCV004244482 pathogenic Stickler syndrome type 1 2023-11-10 criteria provided, single submitter clinical testing PVS1, PS4, PM2
Clinical Biomedical Laboratory, Shriners Hospital For Children - Canada RCV004689424 SCV005088073 pathogenic Stickler syndrome 2024-08-08 criteria provided, single submitter clinical testing This variant is predicted to introduce a premature termination codon in COL2A1. Premature termination codons in COL2A1 are a known cause of Stickler syndrome (PMID: 10982970). This is expected to lead to degradation of the affected transcript and haploinsufficiency. This variant is absent from general population databases (Genome Aggregation Database v2.1.1), indicating it is not a common polymorphism. This specific variant is reported in ClinVar (Variation ID: 17395) as pathogenic from multiple submitters for various conditions including Stickler syndrome type 1. This specific variant has been reported in the literature (PMID: 20179744) and in the Leiden Open Variation database V3.
Ambry Genetics RCV004975261 SCV005568873 pathogenic Inborn genetic diseases 2024-09-30 criteria provided, single submitter clinical testing The c.1957C>T (p.R653*) alteration, located in exon 30 (coding exon 30) of the COL2A1 gene, consists of a C to T substitution at nucleotide position 1957. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 653. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD). This variant was reported in multiple individuals with features consistent with COL2A1-related skeletal dysplasia (Chan, 2023; Fujimoto, 2021; Zhou, 2018). Based on the available evidence, this alteration is classified as pathogenic.
OMIM RCV000018938 SCV000039224 pathogenic Stickler syndrome type 1 2003-09-01 no assertion criteria provided literature only
OMIM RCV000018939 SCV000039225 pathogenic Autosomal dominant rhegmatogenous retinal detachment 2003-09-01 no assertion criteria provided literature only
GeneReviews RCV000018938 SCV000190933 not provided Stickler syndrome type 1 no assertion provided literature only

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