ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2594A>G (p.Tyr865Cys)

gnomAD frequency: 0.00003  dbSNP: rs777842626
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000556974 SCV000623279 uncertain significance Bloom syndrome 2022-10-17 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 865 of the BLM protein (p.Tyr865Cys). This variant is present in population databases (rs777842626, gnomAD 0.004%). 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: 454110). 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. 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.
Mendelics RCV000556974 SCV000838977 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV001015892 SCV001176780 uncertain significance Hereditary cancer-predisposing syndrome 2022-08-22 criteria provided, single submitter clinical testing The p.Y865C variant (also known as c.2594A>G), located in coding exon 12 of the BLM gene, results from an A to G substitution at nucleotide position 2594. The tyrosine at codon 865 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is not well 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.
Natera, Inc. RCV000556974 SCV001454858 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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