Submissions for variant NM_001852.4(COL9A2):c.1400A>G (p.Gln467Arg)

gnomAD frequency: 0.00025  dbSNP: rs373264436

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000372533	SCV000357511	likely benign	Epiphyseal dysplasia, multiple, 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
GeneDx	RCV001315749	SCV000573891	likely benign	not provided	2020-09-11	criteria provided, single submitter	clinical testing
Fulgent Genetics, Fulgent Genetics	RCV000763903	SCV000894844	uncertain significance	Epiphyseal dysplasia, multiple, 2; Stickler syndrome, type 5	2018-10-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000478668	SCV001157048	likely benign	not specified	2018-12-15	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001315749	SCV001506339	likely benign	not provided	2025-01-28	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000478668	SCV004122129	uncertain significance	not specified	2023-10-25	criteria provided, single submitter	clinical testing	Variant summary: COL9A2 c.1400A>G (p.Gln467Arg) results in a conservative amino acid change located in the Collagen triple helix repeat (IPR008160) of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. Consensus agreement among computation tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00048 in 163758 control chromosomes in the gnomAD database, including 1 homozygote. To our knowledge, no occurrence of c.1400A>G in individuals affected with Epiphyseal dysplasia, multiple, 2 and no experimental evidence demonstrating its impact on protein function have been reported. Five submitters have cited clinical-significance assessments for this variant to ClinVar after 2014, and classified it as likely benign (n=4) or uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003940120	SCV004748523	likely benign	COL9A2-related disorder	2019-06-05	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).