Submissions for variant NM_000057.4(BLM):c.2406+2T>G

dbSNP: rs367543016

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV001806715	SCV002050816	likely pathogenic	Bloom syndrome	2021-12-02	criteria provided, single submitter	clinical testing	Variant summary: BLM c.2406+2T>G is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Several computational tools predict a significant impact on normal splicing: Four predict the variant abolishes a canonical 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 251448 control chromosomes (gnomAD). c.2406+2T>G has been reported in the literature in individuals affected with Bloom Syndrome without evidence for causality (example: German_2007). This report does not provide unequivocal conclusions about association of the variant with Bloom Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic.
Baylor Genetics	RCV001806715	SCV004210869	pathogenic	Bloom syndrome	2023-08-11	criteria provided, single submitter	clinical testing