Submissions for variant NM_080680.3(COL11A2):c.2921C>T (p.Ala974Val)

gnomAD frequency: 0.00016  dbSNP: rs376797260

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000155702	SCV000205412	uncertain significance	not specified	2018-05-21	criteria provided, single submitter	clinical testing	The p.Ala974Val variant in COL11A2 has been previously reported by our laborator y in 2 individuals with hearing loss, 1 of whom had an alternate etiology. The v ariant is also present in ClinVar (Variation ID# 178927) and was identified in 0 .02% (21/99192) of European chromosomes by gnomAD (http://gnomad.broadinstitute. org). Although this variant has been seen in the general population, its frequen cy is not high enough to rule out a pathogenic role. Computational prediction to ols and conservation analyses suggest that this variant may not impact the prote in, though this information is not predictive enough to rule out pathogenicity. In summary, the clinical significance of the p.Ala974Val variant is uncertain. ACMG/AMP Criteria applied: BP4.
GeneDx	RCV001537799	SCV000726016	likely benign	not provided	2020-10-02	criteria provided, single submitter	clinical testing
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000680469	SCV000807844	likely benign	Connective tissue disorder	2018-06-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001154083	SCV001315407	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	RCV001154084	SCV001315408	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	RCV001154085	SCV001315410	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001537799	SCV002214986	likely benign	not provided	2024-01-31	criteria provided, single submitter	clinical testing
GenomeConnect, ClinGen	RCV000709936	SCV000840293	not provided	Autosomal recessive nonsyndromic hearing loss 53; Autosomal dominant nonsyndromic hearing loss 13; Otospondylomegaepiphyseal dysplasia, autosomal recessive; Otospondylomegaepiphyseal dysplasia, autosomal dominant; Fibrochondrogenesis 2		no assertion provided	phenotyping only	GenomeConnect assertions are reported exactly as they appear on the patient-provided report from the testing laboratory. GenomeConnect staff make no attempt to reinterpret the clinical significance of the variant.