ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.3556A>G (p.Lys1186Glu)

gnomAD frequency: 0.00004  dbSNP: rs750532596
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000687324 SCV000814887 uncertain significance Bloom syndrome 2024-01-28 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 1186 of the BLM protein (p.Lys1186Glu). This variant is present in population databases (rs750532596, gnomAD 0.05%). 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: 567289). 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 tolerated. RNA analysis performed to evaluate the impact of this missense change on mRNA splicing indicates it does not significantly alter splicing (Invitae). 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 RCV000687324 SCV000838985 uncertain significance Bloom syndrome 2018-07-02 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000687324 SCV000896488 uncertain significance Bloom syndrome 2018-10-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV001020601 SCV001182100 likely benign Hereditary cancer-predisposing syndrome 2021-11-23 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Baylor Genetics RCV000687324 SCV001482838 uncertain significance Bloom syndrome 2020-11-16 criteria provided, single submitter clinical testing This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Sema4, Sema4 RCV001020601 SCV002532466 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-16 criteria provided, single submitter curation
GeneDx RCV002293470 SCV002586806 uncertain significance not provided 2023-06-23 criteria provided, single submitter clinical testing In silico analysis supports that this missense variant does not alter protein structure/function; Observed in at least one individual with breast cancer in published literature (Guindalini et al., 2022); This variant is associated with the following publications: (PMID: 35264596)

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