ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2351A>G (p.Tyr784Cys)

gnomAD frequency: 0.00001  dbSNP: rs753635754
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000540918 SCV000623266 uncertain significance Bloom syndrome 2024-01-17 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 784 of the BLM protein (p.Tyr784Cys). This variant is present in population databases (no rsID available, gnomAD 0.005%). 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: 454100). 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.
Sema4, Sema4 RCV002257781 SCV002529370 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-15 criteria provided, single submitter curation
Ambry Genetics RCV002257781 SCV002733113 uncertain significance Hereditary cancer-predisposing syndrome 2022-07-29 criteria provided, single submitter clinical testing The p.Y784C variant (also known as c.2351A>G), located in coding exon 10 of the BLM gene, results from an A to G substitution at nucleotide position 2351. The tyrosine at codon 784 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly 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.
Fulgent Genetics, Fulgent Genetics RCV000540918 SCV002779954 uncertain significance Bloom syndrome 2021-07-25 criteria provided, single submitter clinical testing
Natera, Inc. RCV000540918 SCV001454852 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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