rs771823715
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Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP7BS2
The NM_003738.5(PTCH2):c.126C>T(p.Gly42=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,822 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000041 ( 0 hom. )
Consequence
PTCH2
NM_003738.5 synonymous
NM_003738.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.157
Genes affected
PTCH2 (HGNC:9586): (patched 2) This gene encodes a transmembrane receptor of the patched gene family. The encoded protein may function as a tumor suppressor in the hedgehog signaling pathway. Alterations in this gene have been associated with nevoid basal cell carcinoma syndrome, basal cell carcinoma, medulloblastoma, and susceptibility to congenital macrostomia. Alternatively spliced transcript variants have been described.[provided by RefSeq, Oct 2009]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -7 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.37).
BP7
Synonymous conserved (PhyloP=0.157 with no splicing effect.
BS2
High AC in GnomAdExome4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
PTCH2 | NM_003738.5 | c.126C>T | p.Gly42= | synonymous_variant | 2/22 | ENST00000372192.4 | NP_003729.3 | |
PTCH2 | NM_001166292.2 | c.126C>T | p.Gly42= | synonymous_variant | 2/23 | NP_001159764.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.126C>T | p.Gly42= | synonymous_variant | 2/22 | 1 | NM_003738.5 | ENSP00000361266 | P2 | |
PTCH2 | ENST00000447098.6 | c.126C>T | p.Gly42= | synonymous_variant | 2/23 | 1 | ENSP00000389703 | A2 |
Frequencies
GnomAD3 genomes Cov.: 32
GnomAD3 genomes
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32
GnomAD3 exomes AF: 0.00000398 AC: 1AN: 251458Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135904
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GnomAD4 exome AF: 0.00000410 AC: 6AN: 1461822Hom.: 0 Cov.: 33 AF XY: 0.00000413 AC XY: 3AN XY: 727208
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GnomAD4 genome Cov.: 32
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Gorlin syndrome Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Mar 10, 2018 | This sequence change affects codon 42 of the PTCH2 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the PTCH2 protein. This variant is present in population databases (rs771823715, ExAC 0.009%). This variant has not been reported in the literature in individuals with PTCH2-related disease. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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. - |
Computational scores
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Name
Calibrated prediction
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at