Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000216559 | SCV000277191 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2015-07-07 | criteria provided, single submitter | clinical testing | The c.988+1delG intronic variant results from a deletion of a G one nucleotide after coding exon 9 of the PMS2 gene. 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. In the ESP, this variant was not observed in 6500 samples (13000 alleles) with coverage at this position. To date, this alteration has been detected with an allele frequency of approximately 0.002% (greater than 65000 alleles tested) in our clinical cohort. This nucleotide position is highly conserved in available vertebrate species. Using two different splice site prediction tools, this alteration is predicted by ESEfinder to weaken the efficacy of the native donor splice site, but is not predicted to have a deleterious effect on this acceptor/donor splice site by BDGP; 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.988+1delG variant is classified as likely pathogenic. |