Submissions for variant NM_000057.4(BLM):c.1722A>G (p.Leu574=)

gnomAD frequency: 0.00379  dbSNP: rs28385011

Total submissions: 15

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000179705	SCV000167186	benign	not specified	2013-10-04	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)	RCV000179705	SCV000231996	likely benign	not specified	2014-08-12	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228415	SCV000283116	benign	Bloom syndrome	2025-02-03	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000571746	SCV000672865	likely benign	Hereditary cancer-predisposing syndrome	2016-09-29	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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	RCV000179705	SCV000918645	benign	not specified	2017-12-25	criteria provided, single submitter	clinical testing	Variant summary: The c.1722A>G (p.Leu574=) in BLM gene is a synonymous change that involves a non-conserved nucleotide. 3/5 programs in Alamut predict that this variant does not affect splicing, however no functional studies supporting this notion were published at the time of evaluation. The variant is present in control dataset of gnomAD at a frequency of 0.0062 (1384/223222 chrs tested, including 16 homozygotes), predominantly in individuals of South Asian descent (0.026; 475/18298 chrs). These frequencies exceed the estimated maximum allele frequency for a pathogenic allele in this gene (0.0035). The variant of interest has been reported as a polymorphism via published reports (German_2007), and is cited as Benign by a reputable databases/clinical laboratories. Taking together, the variant was classified as Benign.
Illumina Laboratory Services, Illumina	RCV000228415	SCV001275085	benign	Bloom syndrome	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.
Genome-Nilou Lab	RCV000228415	SCV001750159	benign	Bloom syndrome	2021-07-01	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000179705	SCV002047007	benign	not specified	2021-05-06	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000228415	SCV002049533	benign	Bloom syndrome	2023-06-14	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000228415	SCV004016392	benign	Bloom syndrome	2023-07-07	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV001725982	SCV005214004	likely benign	not provided		criteria provided, single submitter	not provided
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV000179705	SCV001807764	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001725982	SCV001965315	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000228415	SCV002092391	benign	Bloom syndrome	2017-06-13	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915237	SCV004734686	benign	BLM-related disorder	2019-08-27	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).