Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Eurofins Ntd Llc |
RCV000593974 | SCV000707520 | likely pathogenic | not provided | 2017-04-18 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000593974 | SCV001575218 | likely pathogenic | not provided | 2020-05-30 | criteria provided, single submitter | clinical testing | Glycine residues within the Gly-Xaa-Yaa repeats of the triple helix domain are required for the structure and stability of fibrillar collagens (PMID: 7695699, 8218237, 19344236). In COL2A1, missense variants at these glycine residues are significantly enriched in individuals with disease (PMID: 10612821, 26443184) compared to the general population (ExAC). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant has not been reported in the literature in individuals with COL2A1-related conditions. ClinVar contains an entry for this variant (Variation ID: 501233). This variant is not present in population databases (ExAC no frequency). This sequence change replaces glycine with aspartic acid at codon 1050 of the COL2A1 protein (p.Gly1050Asp). The glycine residue is highly conserved and there is a moderate physicochemical difference between glycine and aspartic acid. |
Institute of Medical Genetics and Genomics, |
RCV001822860 | SCV002072469 | likely pathogenic | Achondrogenesis type II | 2022-01-30 | no assertion criteria provided | clinical testing | The novel heterozygous mis-sense variant c.3149G>A (p.G1050E) has not been observed in gnomAD and 1000g. In-silico bioinformatic software predict this variant by mutation taster as Disease causing and SIFT & PROVEAN as Damaging. The phenotype observed in the proband was flat facies, severe micromelia, short and flared thorax, protuberant abdomen, large and prominent forehead and unossified vertebral bodies. Achondrogenesis type II is an autosomal dominant disorder and based on the phenotypic observation we classify this variant as likely pathogenic. |