1-44827883-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_003738.5(PTCH2):c.2018G>T(p.Arg673Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000601 in 1,614,032 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. R673C) 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.2018G>T | p.Arg673Leu | missense_variant | 14/22 | ENST00000372192.4 | |
PTCH2 | NM_001166292.2 | c.2018G>T | p.Arg673Leu | missense_variant | 14/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.2018G>T | p.Arg673Leu | missense_variant | 14/22 | 1 | NM_003738.5 | P2 | |
PTCH2 | ENST00000447098.6 | c.2018G>T | p.Arg673Leu | missense_variant | 14/23 | 1 | A2 |
Frequencies
GnomAD3 genomes AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 33
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251266Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135840
GnomAD4 exome AF: 0.0000623 AC: 91AN: 1461804Hom.: 0 Cov.: 47 AF XY: 0.0000688 AC XY: 50AN XY: 727196
GnomAD4 genome AF: 0.0000394 AC: 6AN: 152228Hom.: 0 Cov.: 33 AF XY: 0.0000269 AC XY: 2AN XY: 74376
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2023 | This sequence change replaces arginine, which is basic and polar, with leucine, which is neutral and non-polar, at codon 673 of the PTCH2 protein (p.Arg673Leu). 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: 254114). This missense change has been observed in individual(s) with Gorlin syndrome (PMID: 28915250). This variant is present in population databases (rs760548568, gnomAD 0.02%). - |
Oromandibular-limb hypogenesis spectrum Benign:1
Likely benign, no assertion criteria provided | research | CHU Sainte-Justine Research Center, University of Montreal | Aug 12, 2016 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at