Submissions for variant NM_000057.4(BLM):c.2522T>C (p.Ile841Thr)

dbSNP: rs767086502

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Baylor Genetics	RCV003474363	SCV004210879	likely pathogenic	Bloom syndrome	2023-11-06	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003479527	SCV004223404	uncertain significance	not specified	2023-11-07	criteria provided, single submitter	clinical testing	Variant summary: BLM c.2522T>C (p.Ile841Thr) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251310 control chromosomes. c.2522T>C has been reported in the literature in at least one homozygous individual affected with Bloom Syndrome (e.g. Ellis_1995). These data indicate that the variant may be associated with disease. One publication reports experimental evidence showing impaired ATPase and helicase activities in vitro, however, does not provide sufficient evidence to allow convincing conclusions about the variant effect in disease (e.g. Guo_2007). The following publications have been ascertained in the context of this evaluation (PMID: 7585968, 17878217). No submitters have cited clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic.