Submissions for variant NM_000057.4(BLM):c.395G>A (p.Arg132Gln)

gnomAD frequency: 0.00002  dbSNP: rs775197136

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000705324	SCV000834315	uncertain significance	Bloom syndrome	2024-11-02	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 132 of the BLM protein (p.Arg132Gln). This variant is present in population databases (rs775197136, gnomAD 0.005%). This variant has not been reported in the literature in individuals affected with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 581487). An algorithm developed to predict the effect of missense changes on protein structure and function outputs the following: PolyPhen-2: "Benign". The glutamine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Ambry Genetics	RCV001021526	SCV001183153	likely benign	Hereditary cancer-predisposing syndrome	2019-06-26	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.
Sema4, Sema4	RCV001021526	SCV002530785	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-21	criteria provided, single submitter	curation
GeneDx	RCV001579393	SCV003915117	uncertain significance	not provided	2022-10-10	criteria provided, single submitter	clinical testing	Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Genome Diagnostics Laboratory, Amsterdam University Medical Center	RCV001579393	SCV001807067	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001579393	SCV001970289	likely benign	not provided		no assertion criteria provided	clinical testing