Genodermatoses with malignancies
Gene: PTCH2
After reviewing with the Genomics England Clinical Team, it was decided to keep this gene Amber until further evidence is available before demoting/promoting the gene status.Created: 4 Aug 2020, 2:39 p.m. | Last Modified: 4 Aug 2020, 2:39 p.m.
Panel Version: 1.6
Pathogenicity of LoF variants has been questioned in this publication which reports a homozygous individual.Created: 28 Feb 2020, 7:34 a.m. | Last Modified: 28 Feb 2020, 7:34 a.m.
Panel Version: 1.6
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted
Phenotypes
Basal cell nevus syndrome, 109400
Publications
Added watchlist tag. Look out for 3rd case.Created: 15 May 2018, 1:53 p.m.
Comment on list classification: Rating as Amber as pathogenic/likely pathogenic germline variants found in 2 cases.Created: 15 May 2018, 12:26 p.m.
Comment on phenotypes: Added Basal cell nevus syndrome 109400 as a phenotype (another name for Gorlin syndrome)Created: 15 May 2018, 12:26 p.m.
Gorlin syndrome is also known as Basal cell nevus syndrome. In OMIM PTCH2 is associated with Basal cell nevus syndrome based on evidence from Fan et al. (2008) (PMID: 18285427) who report 6 affected members of a Chinese Han family with autosomal dominant basal cell nevus syndrome. A heterozygous 2157G-A transition in the PTCH2 gene, which results in a arg719-to-gln substitution. The mutation was not identified in 520 control individuals. OMIM also reports that somatic mutations in the PTCH2 gene have been identified in basal cell carcinoma (605462) and in medulloblastoma (155255), both of which are features of the nevoid basal cell carcinoma syndrome (Smyth et al. (1999), PMID:9931336). Clinvar reports another pathogenic/likely pathogenic mutation from a patient with Gorlin syndrome - a germline frameshift mutation due to a 2-bp deletion in PTCH2 resulting in a truncated form of the PTCH2 protein reported by Fujii et al 2013 (PMID: 23479190). Pubmed search, Jensen Lab, Orphanet and Gene2Phenotype searches did not find additional cases. Rating as Amber as pathogenic/likely pathogenic germline variants found in 2 cases.Created: 15 May 2018, 11:17 a.m.
Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, imprinted status unknown
Publications
This gene has been classified as Amber List (Moderate Evidence).
Phenotypes for PTCH2 were set to Medulloblastoma; Basal cell carcinoma, somatic; (originally on Gorlin syndrome gene panel); Basal cell nevus syndrome 109400
This gene has been classified as Red List (Low Evidence).
PTCH2 was added to Genodermatoses with malignanciespanel. Sources: Radboud University Medical Center, Nijmegen