Submissions for variant NM_000089.4(COL1A2):c.122G>A (p.Arg41His)

gnomAD frequency: 0.00310  dbSNP: rs139528613

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000371779	SCV000470553	benign	Ehlers-danlos syndrome, arthrochalasia type, 2	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina	RCV000260651	SCV000470554	benign	Osteogenesis imperfecta	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
GeneDx	RCV000443633	SCV000518770	benign	not specified	2016-10-24	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.
Athena Diagnostics	RCV000443633	SCV000612913	benign	not specified	2017-06-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001088162	SCV000627284	benign	Osteogenesis imperfecta type I; Ehlers-Danlos syndrome, classic type, 1	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000757105	SCV000885219	likely benign	not provided	2017-05-21	criteria provided, single submitter	clinical testing	The p.Arg41His variant (rs139528613) was reported as identified by whole exome sequencing in three African-American mothers with premature ruptures of membranes (Modi 2017). However, the p.Arg41His variant has been identified with allele frequency of 1.0 percent (on 242 out of 24,024 chromosomes) in African populations and with an overall population frequency of 0.09 percent (identified on 258 out of 277,154 chromosomes) and in gnomAD browser. Additionally, the p.Arg41His variant is also listed in the ClinVar database with current classification of benign or likely benign (Variation ID 360944).
Genome Diagnostics Laboratory, The Hospital for Sick Children	RCV000260651	SCV002564765	likely benign	Osteogenesis imperfecta	2021-08-13	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002374600	SCV002667389	benign	Cardiovascular phenotype	2020-10-29	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
PreventionGenetics, part of Exact Sciences	RCV003932489	SCV004754111	benign	COL1A2-related disorder	2019-10-25	no assertion criteria provided	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).