chr9-95468829-C-G
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 1P and 7B. PP2BP4_ModerateBP6BS2
The NM_000264.5(PTCH1):āc.2172G>Cā(p.Glu724Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000212 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E724K) has been classified as Likely benign.
Frequency
Consequence
NM_000264.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2172G>C | p.Glu724Asp | missense_variant | 14/24 | ENST00000331920.11 | NP_000255.2 | |
PTCH1 | NM_001083603.3 | c.2169G>C | p.Glu723Asp | missense_variant | 14/24 | ENST00000437951.6 | NP_001077072.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2172G>C | p.Glu724Asp | missense_variant | 14/24 | 5 | NM_000264.5 | ENSP00000332353.6 | ||
PTCH1 | ENST00000437951.6 | c.2169G>C | p.Glu723Asp | missense_variant | 14/24 | 5 | NM_001083603.3 | ENSP00000389744.2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251478Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135910
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1461890Hom.: 0 Cov.: 33 AF XY: 0.0000165 AC XY: 12AN XY: 727244
GnomAD4 genome Cov.: 32
ClinVar
Submissions by phenotype
Basal cell carcinoma, susceptibility to, 1 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | May 16, 2023 | - - |
Hereditary cancer-predisposing syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 04, 2024 | The p.E724D variant (also known as c.2172G>C), located in coding exon 14 of the PTCH1 gene, results from a G to C substitution at nucleotide position 2172. The glutamic acid at codon 724 is replaced by aspartic acid, an amino acid with highly similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Gorlin syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Jan 24, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at