Submissions for variant NM_080680.3(COL11A2):c.544G>A (p.Val182Ile)

gnomAD frequency: 0.00004  dbSNP: rs375937729

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Center for Human Genetics, Inc, Center for Human Genetics, Inc	RCV000659329	SCV000781140	likely benign	Connective tissue disorder	2016-11-01	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000825903	SCV000967388	uncertain significance	not specified	2018-04-25	criteria provided, single submitter	clinical testing	Variant classified as Uncertain Significance - Favor Benign. The p.Val182Ile var iant in COL11A2 has not been previously reported in individuals with hearing los s or COL11A2-related syndromes. This variant has been identified in 8/17130 East Asian chromosomes, including one homozygous individual, by the Genome Aggregati on Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs375937729). Altho ugh this variant has been seen in the general population, its frequency is not h igh enough to rule out a pathogenic role. The valine (Val) at position 182 is no t highly conserved in mammals and evolutionary distant species, and two mammals (opossum and tasmanian devil) carry an isoleucine (Ile) at this position, which suggests that a change at this position may be tolerated. Additional computation al prediction tools and conservation analysis suggest that the p.Val182Ile varia nt may not impact the protein, though this information is not predictive enough to rule out pathogenicity. In summary, while the clinical significance of the p. Val182Ile variant is uncertain, the frequency and conservation data suggest that it is more likely to be benign. ACMG/AMP Criteria applied: BP4
GeneDx	RCV001564237	SCV001787370	uncertain significance	not provided	2020-06-26	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 does not alter protein structure/function
Invitae	RCV001564237	SCV002460016	likely benign	not provided	2024-01-25	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV001564237	SCV003831160	uncertain significance	not provided	2021-12-06	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003163035	SCV003868442	uncertain significance	Inborn genetic diseases	2023-02-28	criteria provided, single submitter	clinical testing	The c.544G>A (p.V182I) alteration is located in exon 4 (coding exon 4) of the COL11A2 gene. This alteration results from a G to A substitution at nucleotide position 544, causing the valine (V) at amino acid position 182 to be replaced by an isoleucine (I). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001564237	SCV004563057	uncertain significance	not provided	2023-05-30	criteria provided, single submitter	clinical testing	The COL11A2 c.544G>A; p.Val182Ile variant (rs375937729), to our knowledge, is not reported in the medical literature but is reported in ClinVar (Variation ID: 547213). This variant is found in the East Asian population with an allele frequency of 0.05% (9/18274 alleles, including 1 homozygote) in the Genome Aggregation Database. Computational analyses predict that this variant is neutral (REVEL: 0.06). However, given the lack of clinical and functional data, the significance of this variant is uncertain at this time.
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001564237	SCV001931121	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001564237	SCV001973278	likely benign	not provided		no assertion criteria provided	clinical testing