rs34245589
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_003738.5(PTCH2):c.2565C>T(p.Leu855=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00191 in 1,614,126 control chromosomes in the GnomAD database, including 105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.0042 ( 20 hom., cov: 33)
Exomes 𝑓: 0.0017 ( 85 hom. )
Consequence
PTCH2
NM_003738.5 synonymous
NM_003738.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.216
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.55).
BP6
?
Variant 1-44827032-G-A is Benign according to our data. Variant chr1-44827032-G-A is described in ClinVar as [Benign]. Clinvar id is 239558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.216 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00416 (634/152326) while in subpopulation AMR AF= 0.0373 (571/15298). AF 95% confidence interval is 0.0348. There are 20 homozygotes in gnomad4. There are 336 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High AC in GnomAd4 at 634 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
PTCH2 | NM_003738.5 | c.2565C>T | p.Leu855= | synonymous_variant | 17/22 | ENST00000372192.4 | |
PTCH2 | NM_001166292.2 | c.2565C>T | p.Leu855= | synonymous_variant | 17/23 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
PTCH2 | ENST00000372192.4 | c.2565C>T | p.Leu855= | synonymous_variant | 17/22 | 1 | NM_003738.5 | P2 | |
PTCH2 | ENST00000447098.6 | c.2565C>T | p.Leu855= | synonymous_variant | 17/23 | 1 | A2 |
Frequencies
GnomAD3 genomes ? AF: 0.00415 AC: 631AN: 152208Hom.: 20 Cov.: 33
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GnomAD3 exomes AF: 0.00715 AC: 1797AN: 251420Hom.: 70 AF XY: 0.00526 AC XY: 715AN XY: 135894
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GnomAD4 exome AF: 0.00168 AC: 2457AN: 1461800Hom.: 85 Cov.: 34 AF XY: 0.00139 AC XY: 1014AN XY: 727204
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GnomAD4 genome ? AF: 0.00416 AC: 634AN: 152326Hom.: 20 Cov.: 33 AF XY: 0.00451 AC XY: 336AN XY: 74488
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ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Gorlin syndrome;C0025149:Medulloblastoma;C2751544:Basal cell carcinoma, susceptibility to, 1 Benign:1
Benign, criteria provided, single submitter | clinical testing | Fulgent Genetics, Fulgent Genetics | Jan 04, 2022 | - - |
Gorlin syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 18, 2024 | - - |
PTCH2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Apr 17, 2019 | This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 24, 2019 | - - |
Computational scores
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Name
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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