ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.808G>A (p.Glu270Lys) (rs762053925)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000541320 SCV000623352 uncertain significance Bloom syndrome 2019-11-20 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid with lysine at codon 270 of the BLM protein (p.Glu270Lys). The glutamic acid residue is weakly conserved and there is a small physicochemical difference between glutamic acid and lysine. This variant is present in population databases (rs762053925, ExAC 0.02%). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 454165). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0". The lysine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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 RCV000570422 SCV000672939 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-12 criteria provided, single submitter clinical testing Insufficient evidence
Integrated Genetics/Laboratory Corporation of America RCV000588275 SCV000694482 uncertain significance not provided 2017-07-21 criteria provided, single submitter clinical testing Variant summary: The c.808G>A (p.Glu270Lys) in BLM gene is a missense variant involves a non-conserved nucleotide and 3/5 in silico tools predict benign outcome, however no functional studies have been published at the time of evaluation. The variant is located within the very N-terminal region of chordate domain, which exact function is not known. The variant is present at a low frequencies in the control population datasets of ExAC and gnomAD (0.00006; 5/120888 and 15/245884 chrs tested, respectively). These frequencies do not exceed the maximal expected allele frequency for a disease causing allele in BLM gene (0.0035). To our knowledge, the variant has not been reported in affected individuals via published reports nor has it been cited by reputable databases/clinical laboratories. Taken together, the variant was classified as VUS, until new information becomes available.

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