Submissions for variant NM_000057.4(BLM):c.2603C>T (p.Pro868Leu)

gnomAD frequency: 0.06742  dbSNP: rs2227935

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000078058	SCV000109896	benign	not specified	2013-03-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000078058	SCV000301738	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000144575	SCV000394420	benign	Bloom syndrome	2018-03-06	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	RCV000568944	SCV000672859	benign	Hereditary cancer-predisposing syndrome	2016-08-12	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	RCV000586013	SCV000694478	benign	not provided	2016-08-31	criteria provided, single submitter	clinical testing	Variant summary: The BLM c.2603C>T (p.Pro868Leu) variant involves the alteration of a conserved nucleotide. 2/2 in silico tools predict a damaging outcome for this variant. This variant was found in 6732/120402 control chromosomes (223 homozygotes) at a frequency of 0.0559127, which is approximately 16 times the estimated maximal expected allele frequency of a pathogenic BLM variant (0.0035355), suggesting this variant is likely a benign polymorphism. Functional studies suggest partial loss of funciton (Mirzaei_2012, Shastri_2015), however the prevalence in the general population as well as numerous homozygous occurrences indicate this variant is insufficient for full-scale Bloom syndrome. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as benign/likely benign. Taken together, this variant is classified as benign.
Invitae	RCV000144575	SCV001000589	benign	Bloom syndrome	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000144575	SCV001623022	benign	Bloom syndrome	2021-05-18	criteria provided, single submitter	clinical testing
GeneDx	RCV000586013	SCV001865926	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing	This variant is associated with the following publications: (PMID: 29484706, 24728327, 24816114, 26788541, 27153395, 19945966, 23129629)
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000144575	SCV002049304	benign	Bloom syndrome	2021-02-04	criteria provided, single submitter	clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center	RCV000144575	SCV004016380	benign	Bloom syndrome	2023-07-07	criteria provided, single submitter	clinical testing
ITMI	RCV000078058	SCV000084373	not provided	not specified	2013-09-19	no assertion provided	reference population
Genetic Services Laboratory, University of Chicago	RCV000078058	SCV000150444	likely benign	not specified		no assertion criteria provided	clinical testing	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed.
Pathway Genomics	RCV000144575	SCV000189874	likely benign	Bloom syndrome	2014-07-24	no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000144575	SCV000733481	benign	Bloom syndrome		no assertion criteria provided	clinical testing
Natera, Inc.	RCV000144575	SCV001190658	benign	Bloom syndrome	2019-05-20	no assertion criteria provided	clinical testing
Natera, Inc.	RCV001824121	SCV001454859	benign	Hereditary disease	2020-09-16	no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000586013	SCV001932382	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000078058	SCV001957523	benign	not specified		no assertion criteria provided	clinical testing