ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2840T>C (p.Ile947Thr)

gnomAD frequency: 0.00003  dbSNP: rs1024172175
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000674804 SCV000800203 uncertain significance Bloom syndrome 2018-05-24 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV000674804 SCV000936869 uncertain significance Bloom syndrome 2023-12-15 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with threonine, which is neutral and polar, at codon 947 of the BLM protein (p.Ile947Thr). This variant is present in population databases (no rsID available, gnomAD 0.008%). 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: 558521). 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 expected to disrupt BLM protein function with a positive 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 RCV001016753 SCV001177746 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-29 criteria provided, single submitter clinical testing The p.I947T variant (also known as c.2840T>C), located in coding exon 14 of the BLM gene, results from a T to C substitution at nucleotide position 2840. The isoleucine at codon 947 is replaced by threonine, an amino acid with similar properties. This amino acid position is poorly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV000674804 SCV002584678 uncertain significance Bloom syndrome 2022-09-28 criteria provided, single submitter clinical testing The BLM c.2840T>C (p.Ile947Thr) missense change has a maximum subpopulation frequency of 0.008% in gnomAD v2.1.1 (https://gnomad.broadinstitute.org). The in silico tool REVEL predicts a deleterious effect on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Bloom syndrome.  In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance. 
Baylor Genetics RCV000674804 SCV004210892 uncertain significance Bloom syndrome 2023-05-11 criteria provided, single submitter clinical testing
Natera, Inc. RCV000674804 SCV001454865 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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