Submissions for variant NM_000057.4(BLM):c.178T>A (p.Leu60Ile)

gnomAD frequency: 0.00007  dbSNP: rs138542210

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Illumina Laboratory Services, Illumina	RCV000330317	SCV000394408	likely 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 likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000330317	SCV000555845	benign	Bloom syndrome	2025-01-29	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000562376	SCV000672886	likely benign	Hereditary cancer-predisposing syndrome	2020-12-17	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.
Cancer Genomics Group, Japanese Foundation For Cancer Research	RCV001030679	SCV001193507	uncertain significance	Hereditary breast ovarian cancer syndrome	2019-05-01	criteria provided, single submitter	research
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800407	SCV002046932	benign	not provided	2021-04-22	criteria provided, single submitter	clinical testing
Genetic Services Laboratory, University of Chicago	RCV000120241	SCV002068919	uncertain significance	not specified	2019-09-09	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000562376	SCV002533647	likely benign	Hereditary cancer-predisposing syndrome	2022-01-19	criteria provided, single submitter	curation
ITMI	RCV000120241	SCV000084389	not provided	not specified	2013-09-19	no assertion provided	reference population
Department of Pediatrics, Samsung Medical Center, Samsung Medical Center	RCV001252853	SCV001163996	uncertain significance	Microcephaly		no assertion criteria provided	research
Natera, Inc.	RCV000330317	SCV001456975	benign	Bloom syndrome	2019-08-06	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV003915190	SCV004734661	likely benign	BLM-related disorder	2020-10-13	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).