rs200366479
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_003738.5(PTCH2):c.703C>T(p.Arg235Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000683 in 1,610,266 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. R235Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_003738.5 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 | UniProt |
---|---|---|---|---|---|---|---|
PTCH2 | NM_003738.5 | c.703C>T | p.Arg235Trp | missense_variant | 6/22 | ENST00000372192.4 | |
PTCH2 | NM_001166292.2 | c.703C>T | p.Arg235Trp | missense_variant | 6/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.703C>T | p.Arg235Trp | missense_variant | 6/22 | 1 | NM_003738.5 | P2 | |
PTCH2 | ENST00000447098.6 | c.703C>T | p.Arg235Trp | missense_variant | 6/23 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000986 AC: 15AN: 152166Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000280 AC: 7AN: 250418Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135508
GnomAD4 exome AF: 0.0000652 AC: 95AN: 1457982Hom.: 0 Cov.: 31 AF XY: 0.0000635 AC XY: 46AN XY: 724752
GnomAD4 genome ? AF: 0.0000985 AC: 15AN: 152284Hom.: 0 Cov.: 31 AF XY: 0.000107 AC XY: 8AN XY: 74464
ClinVar
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 07, 2023 | The c.703C>T (p.R235W) alteration is located in exon 6 (coding exon 6) of the PTCH2 gene. This alteration results from a C to T substitution at nucleotide position 703, causing the arginine (R) at amino acid position 235 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jun 27, 2023 | 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. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt PTCH2 protein function. ClinVar contains an entry for this variant (Variation ID: 524512). This variant has not been reported in the literature in individuals affected with PTCH2-related conditions. This variant is present in population databases (rs200366479, gnomAD 0.008%). This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 235 of the PTCH2 protein (p.Arg235Trp). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at