9-95468896-G-C
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 1P and 5B. PP2BP6BS2
The NM_000264.5(PTCH1):āc.2105C>Gā(p.Pro702Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,614,040 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. P702L) has been classified as Uncertain significance.
Frequency
Consequence
NM_000264.5 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 |
---|---|---|---|---|---|---|---|
PTCH1 | NM_000264.5 | c.2105C>G | p.Pro702Arg | missense_variant | 14/24 | ENST00000331920.11 | |
PTCH1 | NM_001083603.3 | c.2102C>G | p.Pro701Arg | missense_variant | 14/24 | ENST00000437951.6 | |
LOC100507346 | NR_038982.1 | n.834G>C | non_coding_transcript_exon_variant | 4/4 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH1 | ENST00000331920.11 | c.2105C>G | p.Pro702Arg | missense_variant | 14/24 | 5 | NM_000264.5 | A2 | |
PTCH1 | ENST00000437951.6 | c.2102C>G | p.Pro701Arg | missense_variant | 14/24 | 5 | NM_001083603.3 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251422Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135896
GnomAD4 exome AF: 0.0000356 AC: 52AN: 1461884Hom.: 0 Cov.: 33 AF XY: 0.0000261 AC XY: 19AN XY: 727240
GnomAD4 genome AF: 0.0000263 AC: 4AN: 152156Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74320
ClinVar
Submissions by phenotype
not provided Uncertain:2
Uncertain significance, criteria provided, single submitter | clinical testing | GeneDx | Mar 16, 2021 | In silico analysis supports that this missense variant does not alter protein structure/function; Observed in an individual with colon cancer, however additional information as not provided (Chan et al., 2018); Observed in an individual with lung adenocarcinoma who also harbored variants in other cancer related genes (Donner eta l., 2018); This variant is associated with the following publications: (PMID: 30093976, 30032850) - |
Uncertain significance, criteria provided, single submitter | clinical testing | Quest Diagnostics Nichols Institute San Juan Capistrano | Feb 10, 2023 | The frequency of this variant in the general population, 0.000016 (4/251422 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in an individual with colon cancer (PMID: 30093976 (2018)), and in an individual with lung adenocarcinoma who also carried variants in other cancer-associated genes (PMID: 30032850 (2018)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is damaging. Based on the available information, we are unable to determine the clinical significance of this variant. - |
Hereditary cancer-predisposing syndrome Uncertain:1Benign:1
Uncertain significance, criteria provided, single submitter | curation | Sema4, Sema4 | Apr 23, 2021 | - - |
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Apr 13, 2018 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 30, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at