ClinVar Miner

Submissions for variant NM_080680.3(COL11A2):c.1382G>A (p.Gly461Asp) (rs141140798)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000725559 SCV000337783 uncertain significance not provided 2017-09-07 criteria provided, single submitter clinical testing
GeneDx RCV000281273 SCV000535709 uncertain significance not specified 2017-01-05 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the COL11A2 gene. The G461D variant has not been published as a pathogenic variant or been reported as a benign variant to our knowledge. The G461D variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. Additionally, this substitution occurs at a position conserved in mammals. Furthermore, in silico analysis predicts this variant is probably damaging to the protein structure/function. Nevertheless, the NHLBI Exome Sequencing Project and the Exome Aggregation Consortium report G461D was observed in 0.1% of alleles from individuals of European ancestry, indicating it may be a rare benign variant in this population.Therefore, based on the currently available information, it is unclear whether this variant is pathogenic or benign. This result cannot be interpreted for diagnosis or used for family member screening at this time.
Laboratory for Molecular Medicine,Partners HealthCare 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 disease 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 PM2_Moderate
Invitae RCV000725559 SCV001601928 likely benign not provided 2020-10-29 criteria provided, single submitter clinical testing

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