Submissions for variant NM_080680.3(COL11A2):c.1637G>A (p.Arg546Gln)

dbSNP: rs199866657

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000175243	SCV000226692	uncertain significance	not provided	2014-12-08	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151604	SCV001312740	uncertain significance	Otospondylomegaepiphyseal dysplasia, autosomal recessive	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001151605	SCV001312742	uncertain significance	Fibrochondrogenesis 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Illumina Laboratory Services, Illumina	RCV001154613	SCV001315989	uncertain significance	Otospondylomegaepiphyseal dysplasia, autosomal dominant	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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000175243	SCV001472264	likely benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
GeneDx	RCV000175243	SCV002043902	uncertain significance	not provided	2023-11-27	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp	RCV000175243	SCV002385531	likely benign	not provided	2025-01-20	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002516668	SCV003612293	uncertain significance	Inborn genetic diseases	2021-07-13	criteria provided, single submitter	clinical testing	The c.1637G>A (p.R546Q) alteration is located in exon 17 (coding exon 17) of the COL11A2 gene. This alteration results from a G to A substitution at nucleotide position 1637, causing the arginine (R) at amino acid position 546 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000175243	SCV002037238	uncertain significance	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000175243	SCV002037681	uncertain significance	not provided		no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004748624	SCV005341503	uncertain significance	COL11A2-related disorder	2024-09-06	no assertion criteria provided	clinical testing	The COL11A2 c.1637G>A variant is predicted to result in the amino acid substitution p.Arg546Gln. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.041% of alleles in individuals of European (Non-Finnish) descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.