ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.2193+1_2193+9del (rs1060500652)

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Total submissions: 3
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000469408 SCV000790435 likely pathogenic Bloom syndrome 2017-03-24 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000469408 SCV000694476 likely pathogenic Bloom syndrome 2016-08-26 criteria provided, single submitter clinical testing Variant summary: The BLM c.2193+1_2193+9delGTAAGTTAT variant involves the deletion of 9 intronic nucleotides including the highly conserved nucleotides at the +1 and +2 positions. One in silico tool predicts a damaging outcome for this variant and 5/5 in silico splicing prediction tools via Alamut predict the complete loss of a canonical splice acceptor site. This variant is absent in 120322 control chromosomes. The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, due to the potential impact of this variant on splicing, it is classified as likely pathogenic.
Invitae RCV000469408 SCV000543397 likely pathogenic Bloom syndrome 2018-10-03 criteria provided, single submitter clinical testing This sequence change affects a donor splice site in intron 9 of the BLM gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with BLM-related disease. ClinVar contains an entry for this variant (Variation ID: 405328). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in BLM are known to be pathogenic (PMID: 17407155). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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