Submissions for variant NM_080680.3(COL11A2):c.2182A>T (p.Ile728Phe)

gnomAD frequency: 0.00011  dbSNP: rs188490457

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000276412	SCV000462476	likely benign	Stickler Syndrome, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000333898	SCV000462477	uncertain significance	Fibrochondrogenesis 2	2018-01-12	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	RCV000353689	SCV000462478	uncertain significance	Otospondylomegaepiphyseal dysplasia, autosomal recessive	2018-01-12	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	RCV000319359	SCV000462480	likely benign	Otospondylomegaepiphyseal dysplasia, autosomal dominant	2016-06-14	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000602277	SCV000711370	uncertain significance	not specified	2016-12-22	criteria provided, single submitter	clinical testing	The p.Ile728Phe variant in COL11A2 has not been previously reported in individua ls with hearing loss, but has been identified in 0.14% (10/7366) of Latino chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs188490457). Although this variant has been seen in the general populat ion, its frequency is not high enough to rule out a pathogenic role. Computation al prediction tools and conservation analysis suggest that the p.Ile728Phe varia nt may impact the protein, though this information is not predictive enough to d etermine pathogenicity. In summary, the clinical significance of the p.Ile728Phe variant is uncertain.
GeneDx	RCV001559646	SCV001781919	uncertain significance	not provided	2023-10-17	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
Invitae	RCV001559646	SCV002358003	likely benign	not provided	2024-01-18	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV001559646	SCV002563888	uncertain significance	not provided	2023-05-01	criteria provided, single submitter	clinical testing	COL11A2: PM2:Supporting, PP3