ClinVar Miner

Submissions for variant NM_000057.4(BLM):c.1220+3A>G

dbSNP: rs1429490877
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001220808 SCV001392820 pathogenic Bloom syndrome 2023-10-03 criteria provided, single submitter clinical testing This sequence change falls in intron 6 of the BLM gene. It does not directly change the encoded amino acid sequence of the BLM protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. This variant is not present in population databases (gnomAD no frequency). This variant has been observed in individuals with clinical features of Bloom syndrome (PMID: 17407155; Invitae). ClinVar contains an entry for this variant (Variation ID: 949363). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that this variant results in skipping of exon 6 and introduces a premature termination codon (Invitae). The resulting mRNA is expected to undergo nonsense-mediated decay. For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics RCV002365996 SCV002660630 uncertain significance Hereditary cancer-predisposing syndrome 2021-02-11 criteria provided, single submitter clinical testing The c.1220+3A>G intronic variant results from an A to G substitution 3 nucleotides after coding exon 5 in the BLM gene. This alteration has been previously identified in an individual with Bloom syndrome in conjunction with a nonsense alteration, c.814A>T (p.Lys272X); phase (cis or trans) of the two alterations was not determined (German J et al. Hum Mutat, 2007 Aug;28:743-53). This nucleotide position is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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