Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV001025159 | SCV001187294 | likely pathogenic | Hereditary cancer-predisposing syndrome | 2020-12-02 | criteria provided, single submitter | clinical testing | The c.634+3_634+6delAAGT intronic variant, located in intron 6 of the PTEN gene, results from a deletion of 4 nucleotides within intron 6 of the PTEN gene. A different alteration occurring within this deletion region, c.634+5G>A, has been identified in multiple individuals with PTEN hamartoma tumor syndrome (PTHS) (Parisi MA et al. J. Med. Genet., 2001 Jan;38:52-8; Lachlan KL et al. J. Med. Genet., 2007 Sep;44:579-85; Kersseboom R et al. Clin. Genet., 2012 Jun;81:555-62; Boccone L et al. Am. J. Med. Genet. A, 2008 Jan;146A:257-60). An additional alteration occurring within this same region, c.634+2_634+3insC, has demonstrated abnormal splicing in a set of patient RNA samples tested (Ambry internal data). The deleted nucleotide region is well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will weaken the native splice donor site. This variant was not reported in population-based cohorts in the Genome Aggregation Database (gnomAD) (Lek M et al. Nature. 2016 08;536:285-91). Based on the majority of available evidence to date, this variant is likely to be pathogenic. |