ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2119C>T (p.Pro707Ser) (rs146077918)

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Total submissions: 9
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115288 SCV000149197 likely benign not specified 2014-03-03 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Pathway Genomics RCV000172805 SCV000223745 likely benign Bloom syndrome 2014-10-30 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000115288 SCV000337707 likely benign not specified 2015-11-25 criteria provided, single submitter clinical testing
Invitae RCV000172805 SCV000555834 benign Bloom syndrome 2019-12-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000563887 SCV000672872 likely benign Hereditary cancer-predisposing syndrome 2018-07-12 criteria provided, single submitter clinical testing Insufficient evidence;In silico models in agreement (benign);Other data supporting benign classification;Co-occurence with a mutation in another gene that clearly explains a proband's phenotype
Integrated Genetics/Laboratory Corporation of America RCV000115288 SCV000918654 likely benign not specified 2018-10-14 criteria provided, single submitter clinical testing Variant summary: BLM c.2119C>T (p.Pro707Ser) results in a non-conservative amino acid change located in the Helicase superfamily 1/2, ATP-binding domain of the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0017 in 277176 control chromosomes, predominantly at a frequency of 0.0025 within the Non-Finnish European subpopulation in the gnomAD database. This frequency is not significantly higher than expected for a pathogenic variant in BLM causing Bloom Syndrome (0.0017 vs 0.0035), allowing no conclusion about variant significance. c.2119C>T has been reported in the literature in individuals affected with breast cancer and in cohorts from Bloom syndrome registries (German_2007, Sokolenko_2012, Thompson_2012). These report(s) do not provide unequivocal conclusions about association of the variant with Bloom Syndrome. Co-occurrences with other pathogenic variant(s) have been reported in patients with breast cancer who did not manifest a full blown phenotype of Bloom syndrome (BLM c.1642C>T, p.Q548X - twice (Sokolenko_2012), phase not provided). This provides additional supporting evidence for a benign role. A functional study, Mirzaei_2012, evaluated the variants affect on hypersensitivity to the DNA-damaging agent hydroxyurea and found the variant to act comparable to wild-type function. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cites the variant as likely benign/benign. Based on the evidence outlined above, the variant was classified as likely benign.
Mendelics RCV000172805 SCV001139703 likely benign Bloom syndrome 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000857591 SCV001149589 likely benign not provided 2020-03-01 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000172805 SCV001278688 uncertain significance Bloom syndrome 2017-04-27 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance.

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