ClinVar Miner

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

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000563887 SCV000672872 likely benign Hereditary cancer-predisposing syndrome 2017-07-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: 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
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000115288 SCV000337707 likely benign not specified 2015-11-25 criteria provided, single submitter clinical testing
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.
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.
Invitae RCV000172805 SCV000555834 benign Bloom syndrome 2018-01-09 criteria provided, single submitter clinical testing
Pathway Genomics RCV000172805 SCV000223745 likely benign Bloom syndrome 2014-10-30 criteria provided, single submitter clinical testing

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