ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.4205C>T (p.Pro1402Leu)

gnomAD frequency: 0.00001  dbSNP: rs770313956
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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 RCV000693122 SCV000820978 uncertain significance Bloom syndrome 2025-01-22 criteria provided, single submitter clinical testing This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 1402 of the BLM protein (p.Pro1402Leu). This variant is present in population databases (rs770313956, 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: 571872). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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 RCV001022050 SCV001183739 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-17 criteria provided, single submitter clinical testing The p.P1402L variant (also known as c.4205C>T), located in coding exon 21 of the BLM gene, results from a C to T substitution at nucleotide position 4205. The proline at codon 1402 is replaced by leucine, an amino acid with similar 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.
GeneDx RCV003442029 SCV004169785 uncertain significance not provided 2023-05-08 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge; This variant is associated with the following publications: (PMID: 31133068)
Quest Diagnostics Nichols Institute San Juan Capistrano RCV003442029 SCV005624283 uncertain significance not provided 2024-02-08 criteria provided, single submitter clinical testing The BLM c.4205C>T (p.Pro1402Leu) variant has been reported in the published literature in at least one individual with breast and/or ovarian cancer (PMID: 27153395 (2016)) and in a tumor sample of an individual with colorectal cancer (PMID: 32620917 (2020)). The frequency of this variant in the general population, 0.000018 (5/282878 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded conflicting predictions that this variant is benign or damaging. Based on the available information, we are unable to determine the clinical significance of this variant.
Natera, Inc. RCV000693122 SCV002090668 uncertain significance Bloom syndrome 2018-09-03 no assertion criteria provided clinical testing

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