Submissions for variant NM_080680.3(COL11A2):c.3173C>T (p.Pro1058Leu)

gnomAD frequency: 0.00003  dbSNP: rs562253142

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Genetic Services Laboratory, University of Chicago	RCV000503631	SCV000594187	uncertain significance	not specified	2017-03-16	criteria provided, single submitter	clinical testing
GeneDx	RCV000657862	SCV000779622	uncertain significance	not provided	2025-02-11	criteria provided, single submitter	clinical testing	In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Reported in association with orofacial clefts in published literature (PMID: 37350193); This variant is associated with the following publications: (PMID: 37350193)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000657862	SCV000885210	uncertain significance	not provided	2024-01-31	criteria provided, single submitter	clinical testing	The COL11A2 c.3173C>T; p.Pro1058Leu variant (rs562253142), is reported in siblings affected with orofacial clefts, however it was also detected in their unaffected father (Diaz Perez 2023). This variant is reported in ClinVar (Variation ID: 434809) and is found in the general population with an overall allele frequency of 0.004% (10/281,788 alleles) in the Genome Aggregation Database (v2.1.1). Computational analyses predict that this variant is deleterious (REVEL: 0.731). Due to limited information, the clinical significance of this variant is uncertain at this time. References: Diaz Perez KK et al. Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference? Am J Med Genet A. 2023 Oct;191(10):2558-2570. PMID: 37350193.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000657862	SCV002317442	benign	not provided	2024-12-24	criteria provided, single submitter	clinical testing
Revvity Omics, Revvity	RCV000657862	SCV003831158	uncertain significance	not provided	2021-10-13	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000503631	SCV005204564	uncertain significance	not specified	2024-06-20	criteria provided, single submitter	clinical testing	Variant summary: COL11A2 c.3173C>T (p.Pro1058Leu) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 3.6e-05 in 250432 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.3173C>T has been reported in the literature in a family affected with orofacial cleft without cosegregation information and with co-occurring variants in other genes (Diaz Perez_2023). This report does not provide unequivocal conclusions about association of the variant with COL11A2-Related Disorders. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. ClinVar contains an entry for this variant (Variation ID: 434809). Based on the evidence outlined above, the variant was classified as uncertain significance.
PreventionGenetics, part of Exact Sciences	RCV003932823	SCV004750429	uncertain significance	COL11A2-related disorder	2023-12-26	no assertion criteria provided	clinical testing	The COL11A2 c.3173C>T variant is predicted to result in the amino acid substitution p.Pro1058Leu. To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.025% of alleles in individuals of East Asian descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.