Submissions for variant NM_080680.3(COL11A2):c.4652G>A (p.Arg1551Gln)

gnomAD frequency: 0.00077  dbSNP: rs145343609

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000724415	SCV000231896	uncertain significance	not provided	2017-10-13	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000218581	SCV000271605	uncertain significance	not specified	2017-03-20	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Arg1551Gln va riant in COL11A2 has been reported by our laboratory in one individual with hear ing loss. It has also been reported in ClinVar (Variation ID# 198337) as likely benign or of uncertain significance. This variant has been identified in 0.1% (6 7/66340) of European chromosomes by the Exome Aggregation Consortium (ExAC, http ://exac.broadinstitute.org; dbSNP rs145343609). Although this variant has been s een in the general population, its frequency is not high enough to rule out a pa thogenic role. Arginine (Arg) at position 1551 is not conserved in 1 mammal (ten rec) or evolutionarily distant species, supporting that a change at this positio n may be tolerated. Computational prediction tools do not provide strong support for or against an impact to the protein; however, splice prediction tools do su ggest an impact to splicing. In summary, while the clinical significance of the p.Arg1551Gln variant is uncertain, the frequency and conservation data suggest i t is more likely to be benign.
Illumina Laboratory Services, Illumina	RCV000320721	SCV000462251	likely benign	Stickler Syndrome, Dominant	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000377623	SCV000462252	likely benign	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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000328722	SCV000462254	likely 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Laboratory Services, Illumina	RCV000381022	SCV000462255	likely benign	Otospondylomegaepiphyseal dysplasia, autosomal dominant	2016-06-14	criteria provided, single submitter	clinical testing
GeneDx	RCV000724415	SCV000573635	uncertain significance	not provided	2023-07-25	criteria provided, single submitter	clinical testing	Has not been previously published as pathogenic or benign to our knowledge; Observed with a likely pathogenic variant on the opposite allele (in trans) in a patient with a reported history of connective tissue disease referred for genetic testing at GeneDx; At the protein level, in silico analysis supports that this missense variant does not alter protein structure/function; In silico analysis suggests this variant may impact gene splicing. In the absence of RNA/functional studies, the actual effect of this sequence change is unknown.
CeGaT Center for Human Genetics Tuebingen	RCV000724415	SCV001154712	uncertain significance	not provided	2019-03-01	criteria provided, single submitter	clinical testing
Invitae	RCV000724415	SCV001665133	likely benign	not provided	2024-01-29	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000724415	SCV003831159	uncertain significance	not provided	2021-06-30	criteria provided, single submitter	clinical testing
GenomeConnect - Brain Gene Registry	RCV003318364	SCV004012811	not provided	COL11A2- Related Disorder		no assertion provided	phenotyping only	Variant interpreted as Uncertain significance and reported on 06-14-2021 by Lab The Children's Hospital of Philadelphia. Assertions are reported exactly as they appear on the patient provided laboratory report. GenomeConnect does not attempt to reinterpret the variant. The IDDRC-CTSA National Brain Gene Registry (BGR) is a study funded by the U.S. National Center for Advancing Translational Sciences (NCATS) and includes 13 Intellectual and Developmental Disability Research Center (IDDRC) institutions. The study is led by Principal Investigator Dr. Philip Payne from Washington University. The BGR is a data commons of gene variants paired with subject clinical information. This database helps scientists learn more about genetic changes and their impact on the brain and behavior. Participation in the Brain Gene Registry requires participation in GenomeConnect. More information about the Brain Gene Registry can be found on the study website - https://braingeneregistry.wustl.edu/.