ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3031G>A (p.Gly1011Arg)

gnomAD frequency: 0.00004  dbSNP: rs370073229
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000467591 SCV000543334 uncertain significance Bloom syndrome 2024-01-15 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 1011 of the BLM protein (p.Gly1011Arg). This variant is present in population databases (rs370073229, gnomAD 0.006%). 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: 405280). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. 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 RCV001018190 SCV001179389 uncertain significance Hereditary cancer-predisposing syndrome 2023-10-13 criteria provided, single submitter clinical testing The c.3031G>A (p.G1011R) alteration is located in exon 16 (coding exon 15) of the BLM gene. This alteration results from a G to A substitution at nucleotide position 3031, causing the glycine (G) at amino acid position 1011 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear.
Genetic Services Laboratory, University of Chicago RCV001821228 SCV002071806 uncertain significance not specified 2021-08-17 criteria provided, single submitter clinical testing DNA sequence analysis of the BLM gene demonstrated a sequence change, c.3031G>A, in exon 16 that results in an amino acid change, p.Gly1011Arg. This sequence change has been described in the gnomAD database with a frequency of 0.0055% in the East Asian subpopulation (dbSNP rs370073229). The p.Gly1011Arg change affects a moderately conserved amino acid residue located in a domain of the BLM protein that is known to be functional. The p.Gly1011Arg substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This sequence change does not appear to have been previously described in individuals with BLM-related disorders. Due to insufficient evidences and the lack of functional studies, the clinical significance of the p.Gly1011Arg change remains unknown at this time.
Natera, Inc. RCV000467591 SCV001454870 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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