Submissions for variant NM_000057.4(BLM):c.410A>G (p.Lys137Arg)

gnomAD frequency: 0.00434  dbSNP: rs28384988

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000120236	SCV000167181	benign	not specified	2014-02-06	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.
Eurofins Ntd Llc (ga)	RCV000120236	SCV000331616	benign	not specified	2015-07-29	criteria provided, single submitter	clinical testing
Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics	RCV000437672	SCV000511441	likely benign	not provided	2016-05-23	criteria provided, single submitter	clinical testing	Converted during submission to Likely benign.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001079982	SCV000555830	benign	Bloom syndrome	2025-02-04	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000575143	SCV000672877	benign	Hereditary cancer-predisposing syndrome	2018-03-20	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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000120236	SCV000918650	benign	not specified	2018-04-06	criteria provided, single submitter	clinical testing	Variant summary: BLM c.410A>G (p.Lys137Arg) results in a conservative amino acid change located in the Bloom syndrome protein, N-terminal domain of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0014 in 277122 control chromosomes, predominantly at a frequency of 0.014 within the African subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within African control individuals in the gnomAD database is approximately 3.96 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.410A>G in individuals affected with Bloom Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Four 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	RCV000120236	SCV002774090	benign	not specified	2021-06-22	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV001079982	SCV004016397	benign	Bloom syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000437672	SCV005213999	likely benign	not provided		criteria provided, single submitter	not provided
CeGaT Center for Human Genetics Tuebingen	RCV000437672	SCV005431778	likely benign	not provided	2025-03-01	criteria provided, single submitter	clinical testing	BLM: BP4, BS1
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001079982	SCV005879125	likely benign	Bloom syndrome	2024-05-01	criteria provided, single submitter	clinical testing
ITMI	RCV000120236	SCV000084384	not provided	not specified	2013-09-19	no assertion provided	reference population
Natera, Inc.	RCV001079982	SCV001456980	benign	Bloom syndrome	2020-04-23	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000120236	SCV001807450	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000120236	SCV001969558	benign	not specified		no assertion criteria provided	clinical testing