Submissions for variant NM_000089.4(COL1A2):c.1350+11A>T

gnomAD frequency: 0.00140  dbSNP: rs193922160

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000616881	SCV000052243	benign	not specified	2025-01-07	criteria provided, single submitter	clinical testing	Variant summary: COL1A2 c.1350+11A>T alters a nucleotide located at a position not widely known to affect splicing. Consensus agreement among computation tools predict no significant impact on normal splicing (TrAP). However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00079 in 177696 control chromosomes in the gnomAD database, including 3 homozygotes. The observed variant frequency is approximately 28.21 fold of the estimated maximal expected allele frequency for a pathogenic variant in COL1A2 causing Osteogenesis Imperfecta phenotype (2.8e-05). To our knowledge, no occurrence of c.1350+11A>T in individuals affected with Osteogenesis Imperfecta and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 35935). Based on the evidence outlined above, the variant was classified as benign.
GeneDx	RCV000616881	SCV000714134	likely benign	not specified	2018-03-01	criteria provided, single submitter	clinical testing	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Illumina Laboratory Services, Illumina	RCV001160979	SCV001322820	likely benign	Ehlers-danlos syndrome, arthrochalasia type, 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	RCV000029591	SCV001322821	likely benign	Osteogenesis imperfecta	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). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV002054486	SCV002326574	benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2025-01-29	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV002512054	SCV002821823	likely benign	not provided	2023-06-01	criteria provided, single submitter	clinical testing	COL1A2: BS2
Athena Diagnostics	RCV000616881	SCV005622197	benign	not specified	2024-02-06	criteria provided, single submitter	clinical testing