Submissions for variant NM_080680.3(COL11A2):c.1382G>A (p.Gly461Asp)

gnomAD frequency: 0.00045  dbSNP: rs141140798

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000725559	SCV000337783	uncertain significance	not provided	2017-09-07	criteria provided, single submitter	clinical testing
GeneDx	RCV000725559	SCV000535709	uncertain significance	not provided	2023-11-10	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 has a deleterious effect on protein structure/function
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000281273	SCV000711006	uncertain significance	not specified	2017-11-02	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Gly461Asp var iant in COL11A2 has been previously reported by our laboratory in 2 families wit h hearing loss; however, it did not segregate with hearing loss in one of the fa milies. This variant has been identified in several populations including in 29/ 34412 Latino chromosomes and 87/126550 of European chromosomes by the Genome Ag gregation Consortium (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs14114079 8). Although this variant has been seen in the general population, its frequency is not high enough to rule out a pathogenic role. Computational prediction tool s and conservation analyses do not provide strong support for or against an impa ct to the protein. In summary, while the clinical significance of the p.Gly461As p variant is uncertain, the population frequency and non-segregation data sugges t that it is more likely to be benign. ACMG/AMP criteria applied: BS4, BS1_Suppo rting.
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659333	SCV000781144	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Department of Otolaryngology – Head & Neck Surgery, Cochlear Implant Center	RCV001375359	SCV001572125	uncertain significance	Hearing impairment	2021-04-12	criteria provided, single submitter	clinical testing	PP3_Supporting
Invitae	RCV000725559	SCV001601928	likely benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000725559	SCV004032667	uncertain significance	not provided	2023-07-01	criteria provided, single submitter	clinical testing	COL11A2: PP3, BS1:Supporting