ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1396G>A (p.Gly466Arg)

gnomAD frequency: 0.00003  dbSNP: rs747760482
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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV001011353 SCV001171662 uncertain significance Hereditary cancer-predisposing syndrome 2023-03-26 criteria provided, single submitter clinical testing The p.G466R variant (also known as c.1396G>A), located in coding exon 6 of the BLM gene, results from a G to A substitution at nucleotide position 1396. The glycine at codon 466 is replaced by arginine, an amino acid with dissimilar properties. This amino acid position is poorly 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV001832332 SCV002151954 uncertain significance Bloom syndrome 2022-03-08 criteria provided, single submitter clinical testing This sequence change replaces glycine, which is neutral and non-polar, with arginine, which is basic and polar, at codon 466 of the BLM protein (p.Gly466Arg). This variant is present in population databases (rs747760482, gnomAD 0.002%). 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: 819099). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The arginine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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.
Natera, Inc. RCV001832332 SCV002090033 uncertain significance Bloom syndrome 2020-03-27 no assertion criteria provided clinical testing

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