Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000564020 | SCV000674643 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2016-02-16 | criteria provided, single submitter | clinical testing | The c.756_756+2delGGTinsTG intronic variant results from a deletion of three nucleotides and an insertion of two nucleotides at the splice junction boundary of coding exon 5 and intron 5. This variant was not reported in population-based cohorts in the following databases: Database of Single Nucleotide Polymorphisms (dbSNP), NHLBI Exome Sequencing Project (ESP) and 1000 Genomes Project. To date, this alteration has been detected with an allele frequency of approximately 0.001% (greater than 120000 alleles tested) in our clinical cohort. This nucleotide region is highly conserved in available vertebrate species. Using the BDGP and ESEfinder splice site prediction tools, this alteration is predicted to abolish the native splice donor site; however, direct evidence is unavailable. Alterations that disrupt the canonical splice donor site are typically deleterious in nature (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294). As such, the c.756_756+2delGGTinsTG variant is classified as likely pathogenic. |