ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2200G>T (p.Ala734Ser)

dbSNP: rs1301298294
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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 RCV001014755 SCV001175506 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-27 criteria provided, single submitter clinical testing The c.2200G>T variant (also known as p.A734S), located in coding exon 9 of the BLM gene, results from a G to T substitution at nucleotide position 2200. The alanine at codon 734 is replaced by serine, an amino acid with similar properties. This nucleotide position is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will result in the creation or strengthening of a novel splice acceptor site. RNA studies have demonstrated that this alteration does not result in abnormal splicing in the set of samples tested (Ambry internal data). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001205235 SCV001376476 uncertain significance Bloom syndrome 2025-01-12 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with serine, which is neutral and polar, at codon 734 of the BLM protein (p.Ala734Ser). This variant is present in population databases (no rsID available, gnomAD 0.0009%). This missense change has been observed in individual(s) with clinical features of BLM-related conditions (PMID: 33850299). ClinVar contains an entry for this variant (Variation ID: 820876). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BLM protein function with a negative predictive value of 80%. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (internal data). 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. RCV001205235 SCV001461837 uncertain significance Bloom syndrome 2020-09-16 no assertion criteria provided clinical testing

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