ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.274A>G (p.Asn92Asp)

gnomAD frequency: 0.00015  dbSNP: rs200690226
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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000656777 SCV000149209 uncertain significance not provided 2024-12-11 criteria provided, single submitter clinical testing In silico analysis indicates that this missense variant does not alter protein structure/function; Observed in the heterozygous and homozygous state in patients with breast cancer (PMID: 30262796, 35264596); This variant is associated with the following publications: (PMID: 35264596, 30262796)
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000203080 SCV000257607 uncertain significance not specified 2015-06-19 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000462198 SCV000543356 benign Bloom syndrome 2025-01-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV000561733 SCV000672866 uncertain significance Hereditary cancer-predisposing syndrome 2022-11-16 criteria provided, single submitter clinical testing The p.N92D variant (also known as c.274A>G), located in coding exon 2 of the BLM gene, results from an A to G substitution at nucleotide position 274. The asparagine at codon 92 is replaced by aspartic acid, an amino acid with highly similar properties. This variant has been reported in 1/327 Mexican patients with a personal and/or family history suspicious for hereditary breast and ovarian cancer syndrome; this individual was homozygous for the variant but additional clinical information was not provided (Quezada Urban R et al. Cancers (Basel), 2018 Sep;10:). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Mendelics RCV000462198 SCV000838945 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000462198 SCV000894957 uncertain significance Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Pars Genome Lab RCV000462198 SCV001652871 uncertain significance Bloom syndrome 2021-05-18 criteria provided, single submitter clinical testing
Institute for Clinical Genetics, University Hospital TU Dresden, University Hospital TU Dresden RCV000656777 SCV002010762 uncertain significance not provided 2021-11-03 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000203080 SCV002069570 uncertain significance not specified 2022-01-18 criteria provided, single submitter clinical testing DNA sequence analysis of the BLM gene demonstrated a sequence change, c.274A>G, in exon 3 that results in an amino acid change, p.Asn92Asp. This sequence change has been described in the gnomAD database with a frequency of 0.023% in the non-Finnish European subpopulation (dbSNP rs200690226). The p.Asn92Asp change affects a poorly conserved amino acid residue located in a domain of the BLM protein that is not known to be functional. The p.Asn92Asp substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change has previously described in an individual with breast cancer (PMID: 30262796). Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Asn92Asp change remains unknown at this time.
Sema4, Sema4 RCV000561733 SCV002529514 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-13 criteria provided, single submitter curation
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000656777 SCV004222463 uncertain significance not provided 2024-08-01 criteria provided, single submitter clinical testing The BLM c.274A>G (p.Asn92Asp) variant has been reported in the published literature in an individual with breast cancer (PMID: 35264596 (2022)). This variant has also been reported in an individual homozygous for the variant and suspected of hereditary breast and ovarian cancer syndrome (PMID: 30262796 (2018)). The frequency of this variant in the general population, 0.00043 (5/11600 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000462198 SCV001456977 uncertain significance Bloom syndrome 2018-05-29 no assertion criteria provided clinical testing

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