rs369481564
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The ENST00000372192.4(PTCH2):c.1663C>T(p.Arg555Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000109 in 1,461,762 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R555Q) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000372192.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTCH2 | NM_003738.5 | c.1663C>T | p.Arg555Trp | missense_variant | 13/22 | ENST00000372192.4 | NP_003729.3 | |
PTCH2 | NM_001166292.2 | c.1663C>T | p.Arg555Trp | missense_variant | 13/23 | NP_001159764.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.1663C>T | p.Arg555Trp | missense_variant | 13/22 | 1 | NM_003738.5 | ENSP00000361266 | P2 | |
PTCH2 | ENST00000447098.6 | c.1663C>T | p.Arg555Trp | missense_variant | 13/23 | 1 | ENSP00000389703 | A2 |
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 exomes AF: 0.0000319 AC: 8AN: 250664Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135584
GnomAD4 exome AF: 0.0000109 AC: 16AN: 1461762Hom.: 0 Cov.: 37 AF XY: 0.0000124 AC XY: 9AN XY: 727174
GnomAD4 genome Cov.: 33
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jun 24, 2021 | This variant has not been reported in the literature in individuals with PTCH2-related disease. This variant is present in population databases (rs369481564, ExAC 0.01%). This sequence change replaces arginine with tryptophan at codon 555 of the PTCH2 protein (p.Arg555Trp). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and tryptophan. Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). 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