Submissions for variant NM_001844.5(COL2A1):c.2114G>A (p.Gly705Asp)

dbSNP: rs2136551606

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Institute of Medical Genetics and Genomics, Sir Ganga Ram Hospital	RCV001822977	SCV002072472	likely pathogenic	Achondrogenesis type II	2022-01-30	no assertion criteria provided	clinical testing	The novel heterozygous mis-sense variant c.2114G>A (p.G705D) 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 short long bones with narrow thorax, short spine and bilateral club feet, flat facial profile with depressed nasal bridge, short nose, retro-micrognathia, rhizomesomelic shortening of all limbs, glossoptosis and large cleft palate. Achondrogenesis type II is an autosomal dominant disorder and based on the phenotypic observation we classify this variant as likely pathogenic.
PreventionGenetics, part of Exact Sciences	RCV004728836	SCV005339590	likely pathogenic	COL2A1-related disorder	2024-06-19	no assertion criteria provided	clinical testing	The COL2A1 c.2114G>A variant is predicted to result in the amino acid substitution p.Gly705Asp. This variant was reported in one individual with autosomal dominant skeletal dysplasia (https://softgenetics.com/PDF/AMP2013_MJ-Basehore.pdf). A different variant affecting the same amino acid (p.Gly705Ser) was reported in the heterozygous condition in one individual with mild spondyloepiphyseal dysplasia (Takagi et al. 2016. PubMed ID: 26586363). The p.Gly705Asp variant affects a Gly residue of the conserved triple helical domain, where substitutions of the glycine are usually pathogenic (Barat-Houari et al. 2016. PubMed ID: 26626311). This variant has not been reported in a large population database, indicating this variant is rare. This variant is interpreted as likely pathogenic.