Submissions for variant NM_080680.3(COL11A2):c.2254G>A (p.Val752Met)

gnomAD frequency: 0.00016  dbSNP: rs201076557

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680471	SCV000807846	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001151377	SCV001312498	benign	Otospondylomegaepiphyseal dysplasia, autosomal recessive	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Illumina Laboratory Services, Illumina	RCV001151378	SCV001312500	uncertain significance	Otospondylomegaepiphyseal dysplasia, autosomal dominant	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Illumina Laboratory Services, Illumina	RCV001151379	SCV001312501	uncertain significance	Fibrochondrogenesis 2	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.
Invitae	RCV001475501	SCV001679691	likely benign	not provided	2024-01-22	criteria provided, single submitter	clinical testing
GeneDx	RCV001475501	SCV001787362	uncertain significance	not provided	2023-09-05	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; In silico analysis supports that this missense variant does not alter protein structure/function
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002298737	SCV002598987	uncertain significance	not specified	2022-09-25	criteria provided, single submitter	clinical testing	Variant summary: COL11A2 c.2254G>A (p.Val752Met) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00014 in 247050 control chromosomes (gnomAD), predominantly at a frequency of 0.00028 within the Non-Finnish European subpopulation in the gnomAD database. c.2254G>A has been reported in the literature in at least one individual affected with hearing loss (Sommen_2016). The variant was also found in the homozygous state in an individual with facial dysmorphology, intellectual disability/developmental delay, muscle weakness and pain, and poor growth; this individual also carried a de novo pathogenic variant in QRICH1 (c.1953dup, p.Arg652fs) which was concordant with their observed phenotype (Ververi_2018). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five ClinVar submitters have assessed the variant since 2014: two classified the variant as uncertain significance, two as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign.
CeGaT Center for Human Genetics Tuebingen	RCV001475501	SCV004185346	uncertain significance	not provided	2023-11-01	criteria provided, single submitter	clinical testing	COL11A2: PM2