Submissions for variant NM_000057.4(BLM):c.615G>A (p.Lys205=)

gnomAD frequency: 0.00496  dbSNP: rs28903082

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000123841	SCV000167184	benign	not specified	2014-01-06	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.
Invitae	RCV000234095	SCV000283152	benign	Bloom syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000123841	SCV000593632	benign	not specified	2019-04-25	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000573446	SCV000672868	likely benign	Hereditary cancer-predisposing syndrome	2016-11-25	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000123841	SCV000916685	benign	not specified	2018-08-13	criteria provided, single submitter	clinical testing	Variant summary: BLM c.615G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0016 in 276156 control chromosomes, predominantly within the African subpopulation at a frequency of 0.017 in the gnomAD database, including 3 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 4.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in BLM causing Bloom Syndrome phenotype (0.0035), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African origin. To our knowledge, no occurrence of c.615G>A in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000123841	SCV002047102	benign	not specified	2021-05-17	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000234095	SCV004016396	benign	Bloom syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV000234095	SCV002089953	likely benign	Bloom syndrome	2017-04-25	no assertion criteria provided	clinical testing