ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.696C>A (p.Ser232Arg) (rs201845548)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115322 SCV000149231 uncertain significance not provided 2014-02-18 criteria provided, single submitter clinical testing Single pathogenic variants in BLM have only recently been described in association with cancer predisposition and the risks are not well understood. This variant is denoted BLM c.696C>A at the cDNA level, p.Ser232Arg (S232R) at the protein level, and results in the change of a Serine to an Arginine (AGC>AGA). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BLM Ser232Arg was not observed at significant allele frequency in the NHLBI Exome Sequencing Project. This variant is a semi-conservative substitution in which a neutral polar amino acid is replaced with a positive polar one, altering a position that is only moderately conserved throughout evolution and is not located in a known functional domain (UniProt). In silico analyses predict this variant to have a benign effect on protein structure and function. On a molecular level, the impact of this missense variant on protein structure and function is not known and thus we consider this to be a variant of uncertain significance. Furthermore, based on the currently available information, cancer risks associated with this variant, and with single variants the BLM gene in general, remain unclear.
Illumina Clinical Services Laboratory,Illumina RCV000326657 SCV000394411 uncertain significance Bloom syndrome 2018-01-12 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease.
Invitae RCV000326657 SCV000623347 likely benign Bloom syndrome 2019-12-26 criteria provided, single submitter clinical testing
Ambry Genetics RCV001025851 SCV001188122 uncertain significance Hereditary cancer-predisposing syndrome 2019-07-01 criteria provided, single submitter clinical testing Insufficient evidence

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