Submissions for variant NM_000057.4(BLM):c.419A>G (p.Glu140Gly)

gnomAD frequency: 0.00958  dbSNP: rs35886055

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000120237	SCV000167182	benign	not specified	2013-10-25	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.
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000224918	SCV000281579	benign	not provided	2014-09-15	criteria provided, single submitter	clinical testing
Invitae	RCV000234547	SCV000283149	benign	Bloom syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000234547	SCV000394409	benign	Bloom syndrome	2018-01-12	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.
Ambry Genetics	RCV000570211	SCV000672879	benign	Hereditary cancer-predisposing syndrome	2016-09-29	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000224918	SCV000694480	benign	not provided	2016-08-31	criteria provided, single submitter	clinical testing	Variant summary: The BLM c.419A>G (p.Glu140Gly) variant involves the alteration of a conserved nucleotide. 3/4 in silico tools predict a benign outcome for this variant (SNPs&GO not captured due to low reliability index). This variant was found in 351/121252 control chromosomes (2 homozygotes), predominantly observed in the African subpopulation at a frequency of 0.0317352 (327/10304). This frequency is about 9 times the estimated maximal expected allele frequency of a pathogenic BLM variant (0.0035355), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Taken together, the variant is classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000120237	SCV002774101	benign	not specified	2021-07-09	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000234547	SCV004016387	benign	Bloom syndrome	2023-07-07	criteria provided, single submitter	clinical testing
ITMI	RCV000120237	SCV000084385	not provided	not specified	2013-09-19	no assertion provided	reference population
Natera, Inc.	RCV000234547	SCV002089924	benign	Bloom syndrome	2017-06-13	no assertion criteria provided	clinical testing