1-44822521-A-AG
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_003738.5(PTCH2):c.3505dupC(p.Leu1169ProfsTer11) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000242 in 1,610,846 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_003738.5 frameshift
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -4 ACMG points.
Transcripts
RefSeq
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.3505dupC | p.Leu1169ProfsTer11 | frameshift_variant | Exon 22 of 22 | 1 | NM_003738.5 | ENSP00000361266.3 | ||
PTCH2 | ENST00000447098.6 | c.3425+80dupC | intron_variant | Intron 22 of 22 | 1 | ENSP00000389703.2 | ||||
PTCH2 | ENST00000438067.5 | c.185+80dupC | intron_variant | Intron 3 of 4 | 3 | ENSP00000413169.1 |
Frequencies
GnomAD3 genomes AF: 0.0000527 AC: 8AN: 151688Hom.: 0 Cov.: 32
GnomAD4 exome AF: 0.0000212 AC: 31AN: 1459158Hom.: 0 Cov.: 32 AF XY: 0.0000234 AC XY: 17AN XY: 725868
GnomAD4 genome AF: 0.0000527 AC: 8AN: 151688Hom.: 0 Cov.: 32 AF XY: 0.0000540 AC XY: 4AN XY: 74092
ClinVar
Submissions by phenotype
Gorlin syndrome Uncertain:1
This sequence change creates a premature translational stop signal (p.Leu1169Profs*11) in the PTCH2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 35 amino acid(s) of the PTCH2 protein. The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This variant has not been reported in the literature in individuals affected with PTCH2-related conditions. ClinVar contains an entry for this variant (Variation ID: 2900989). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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. -
not provided Uncertain:1
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Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at