Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000665548 | SCV000789690 | uncertain significance | Bloom syndrome | 2017-02-09 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000665548 | SCV001400594 | uncertain significance | Bloom syndrome | 2019-10-24 | criteria provided, single submitter | clinical testing | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with BLM-related conditions. ClinVar contains an entry for this variant (Variation ID: 550724). This variant is not present in population databases (ExAC no frequency). This sequence change falls in intron 2 of the BLM gene. It does not directly change the encoded amino acid sequence of the BLM protein, but it affects a nucleotide within the consensus splice site of the intron. |
| Ambry Genetics | RCV002386142 | SCV002693515 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-10-27 | criteria provided, single submitter | clinical testing | The c.98+3_98+6delAAGT intronic variant, located in intron 1 of the BLM gene, results from a deletion of 4 nucleotides (AAGT) at positions c.98+3 to c.98+6 in intron 1 of the BLM gene. This nucleotide region is highly conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. Another alteration at the same donor site (c.98+1G>T) with the same predicted splicing impact has been reported in a compound heterozygous state with the Ashkenazi founder mutation (c.2207_2212delinsTAGATTC) in a child with Bloom syndrome (German J et al. Hum. Mutat. 2007 Aug;28(8):743-53). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |