chr1-44830923-G-C
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_003738.5(PTCH2):c.738C>G(p.Ala246Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000276 in 1,447,390 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Synonymous variant affecting the same amino acid position (i.e. A246A) has been classified as Likely benign.
Frequency
Consequence
NM_003738.5 synonymous
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Uncertain_significance. Variant got 2 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.738C>G | p.Ala246Ala | synonymous_variant | Exon 6 of 22 | 1 | NM_003738.5 | ENSP00000361266.3 | ||
PTCH2 | ENST00000447098.6 | c.738C>G | p.Ala246Ala | synonymous_variant | Exon 6 of 23 | 1 | ENSP00000389703.2 |
Frequencies
GnomAD3 genomes Cov.: 31
GnomAD3 exomes AF: 0.00000403 AC: 1AN: 248434Hom.: 0 AF XY: 0.00 AC XY: 0AN XY: 134476
GnomAD4 exome AF: 0.00000276 AC: 4AN: 1447390Hom.: 0 Cov.: 31 AF XY: 0.00000139 AC XY: 1AN XY: 717404
GnomAD4 genome Cov.: 31
ClinVar
Submissions by phenotype
PTCH2-related disorder Uncertain:1
The PTCH2 c.738C>G variant is not predicted to result in an amino acid change (p.=). This variant is predicted to alter splicing based on available splicing prediction programs (SpliceAI, Jaganathan et al. 2019. PubMed ID: 30661751). To our knowledge, this variant has not been reported in the literature. This variant is reported in 0.0029% of alleles in individuals of Latino descent in gnomAD and is classified as a variant of uncertain significance in ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/variation/1403063/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. -
Gorlin syndrome Uncertain:1
This sequence change affects codon 246 of the PTCH2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PTCH2 protein. This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with PTCH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1403063). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at