About PTCH1
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTCH1 c.113G>A, p.(Gly38Glu)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely benign classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is Not recorded. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 0
Benign evidence criteria: 4
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 4
BS2Supporting
BS2 · supporting
The variant has been observed in a healthy adult heterozygous carrier: the mother of the proband in PMID:29230040 carries the variant and has no cancer history, with an unremarkable family history spanning three generations. Additionally, the variant is present in gnomAD population databases (200 alleles in v4.1), indicating it is tolerated in the general population.
BS4Supporting
BS4 · supporting
The variant does not segregate with disease in the only reported family (PMID:29230040). The variant was inherited from the mother, who has no personal or family history of Gorlin syndrome-associated features across three generations, while the proband presented with congenital embryonal rhabdomyosarcoma. This lack of segregation supports a benign interpretation.
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on gene product: REVEL score 0.162 (benign range, below 0.5 threshold), BayesDel score -0.434 (negative, predicting benign), and SpliceAI max delta score 0.02 (no predicted splicing impact).
BP6Supporting
BP6 · supporting
Multiple clinical laboratories have classified this variant as Likely benign or Benign in ClinVar (variation ID 216367): 4 labs report Likely benign, 1 reports Benign. Only 2 report Uncertain significance. No submitter reports Pathogenic or Likely pathogenic.
Recorded classification: Likely benign
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: BS2 supporting benign, BS4 supporting benign, BP4 supporting benign, BP6 supporting benign; combination = 4 supporting benign, which maps to Likely Benign.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
200 / 1,603,018 alleles
gnomAD v4.1: 200 / 1,603,018 alleles. Recorded AF 0.000124765. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.62983e-05; MAF= 0.00963%, 25/259610 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000161881; MAF= 0.01619%, 19/117370 alleles, homozygotes = 0); grpmax FAF= 9.09e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0003266906239790918, 6/18366 alleles, homozygotes = 0).
SpliceAI score
0.020 maximum delta
Recorded SpliceAI maximum delta score: 0.020. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
7 reported laboratory submissions
4 Likely benign · 2 Uncertain significance · 1 Benign. ClinVar API review status: criteria provided, conflicting classifications.
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PTCH1, a tumor suppressor and inhibitor of the hedgehog pathway, is recurrently mutated in basal cell carcinoma.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
3 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV59494982, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 4 met · 21 not met · 0 not assessed · 1 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000264.5:c.113G>A (p.Gly38Glu) is a missense variant in PTCH1. PVS1 is not applicable as the variant does not fall into a null-variant class.
This variant is present in gnomAD population databases at frequencies (v2.1 AF=0.0096%, 25 alleles; v4.1 AF=0.0125%, 200 alleles) that exceed the maximum credible allele frequency for Gorlin syndrome (prevalence ~1/50,000-1/256,000), arguing against a highly penetrant pathogenic role.
Multiple in silico predictors consistently suggest a benign effect: REVEL score 0.162, BayesDel score -0.434, and SpliceAI max delta 0.02 (BP4).
The variant has been observed in a healthy adult carrier (mother of proband in Taeubner et al. 2018, PMID:29230040) who is heterozygous for PTCH1 p.G38E with no personal or family cancer history across three generations (BS2).
The variant does not segregate with Gorlin syndrome features in the only reported family: the variant-carrying mother is unaffected, and the proband's congenital embryonal rhabdomyosarcoma occurred in the context of a co-occurring PTCH2 variant (BS4).
Multiple clinical laboratories in ClinVar have classified this variant as Likely benign (4 labs) or Benign (1 lab), with only 2 reporting Uncertain significance and none reporting Pathogenic/Likely pathogenic (BP6).
No pathogenic criteria are met. Applying the ACMG/AMP 2015 combination rules: 4 supporting benign criteria (BS2, BS4, BP4, BP6) are fulfilled, which classifies this variant as Likely benign.
No criteria match.
Met · 4
BS2 SupportingThe variant has been observed in a healthy adult heterozygous carrier: the mother of the proband in PMID:29230040 carries the variant and has no cancer history, with an unremarkable family history spanning three generations. Additionally, the variant is present in gnomAD population databases (200 alleles in v4.1), indicating it is tolerated in the general population. Details ▾Hide ▴
Evidence considered
- Healthy adult carrier (mother in PMID:29230040) heterozygous for PTCH1 p.G38E. No cancer history
- unremarkable family history for 3 generations. Present in gnomAD v4.1 at 200 alleles.
Still missing
- Gorlin syndrome has age-dependent penetrance
- the mother could theoretically develop features later
- but the family history over 3 generations supports benign classification.
Sources
BS4 SupportingThe variant does not segregate with disease in the only reported family (PMID:29230040). The variant was inherited from the mother, who has no personal or family history of Gorlin syndrome-associated features across three generations, while the proband presented with congenital embryonal rhabdomyosarcoma. This lack of segregation supports a benign interpretation. Details ▾Hide ▴
Evidence considered
- Variant-carrier mother unaffected
- unremarkable family history for 3 generations. Proband phenotype (congenital eRMS) not clearly attributable to PTCH1 p.G38E alone given co-occurring PTCH2 variant.
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product: REVEL score 0.162 (benign range, below 0.5 threshold), BayesDel score -0.434 (negative, predicting benign), and SpliceAI max delta score 0.02 (no predicted splicing impact). Details ▾Hide ▴
Evidence considered
- REVEL=0.162 (benign)
- BayesDel=-0.434 (benign)
- SpliceAI max delta=0.02 (no splicing impact). Multiple concordant in silico predictions of benign effect.
Sources
BP6 SupportingMultiple clinical laboratories have classified this variant as Likely benign or Benign in ClinVar (variation ID 216367): 4 labs report Likely benign, 1 reports Benign. Only 2 report Uncertain significance. No submitter reports Pathogenic or Likely pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar variation 216367: Likely benign (4 labs)
- Benign (1 lab)
- VUS (2 labs). Majority clinical consensus supports benign interpretation.
Still missing
- No expert panel review (ClinGen VCEP) available for PTCH1 to corroborate clinical laboratory classifications.
Sources
Not met · 21 · evaluated, threshold not reached
PVS1 NM_000264.5:c.113G>A is a missense variant (p.Gly38Glu), not a null variant (nonsense, frameshift, or canonical splice site). Per ClinGen SVI PVS1 recommendations (PMC6185798), PVS1 is not applicable to missense variants. Details ▾Hide ▴
Evidence considered
- Missense substitution at c.113
- variant bucket: other
- not eligible for PVS1 under ClinGen SVI framework.
Sources
pvs1_generic_framework ↗pvs1_variant_assessment
PS1 No alternate nucleotide change at the same amino acid position (p.Gly38) has been reported as pathogenic. No data available to support PS1. Details ▾Hide ▴
Evidence considered
- No evidence of a different pathogenic nucleotide substitution at codon 38 identified.
PS2 The variant was inherited from the mother, as confirmed by trio whole-exome sequencing in PMID:29230040. It is not a de novo occurrence. Details ▾Hide ▴
Evidence considered
- Trio WES confirmed maternal inheritance
- 'The PTCH1 mutation p.(Gly38Glu) is inherited from the mother' (Taeubner et al. 2018).
Sources
PS3 No variant-specific functional assay demonstrating a deleterious effect has been performed. The qRT-PCR data from PMID:29230040 measures patient-derived expression levels, not a controlled functional characterization of the variant. In silico predictors (REVEL 0.162, BayesDel -0.434) are in the benign range. Details ▾Hide ▴
Evidence considered
- Patient-derived qRT-PCR from PMID:29230040 showed decreased PTCH1 expression but is not a controlled functional assay. REVEL score 0.162 and BayesDel score -0.434 predict benign.
Still missing
- No controlled in vitro functional assay for p.G38E.
Sources
PS4 The variant is present in gnomAD population databases at frequencies (v2.1: 0.0096%, v4.1: 0.0125%) that are inconsistent with a highly penetrant pathogenic variant for Gorlin syndrome (prevalence ~1/50,000-1/256,000). No case-control data demonstrating enrichment in affected individuals exists. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.0096% (25/259
- 610 alleles)
- gnomAD v4.1 AF=0.0125% (200/1
- 603
- 018 alleles). Frequency exceeds maximum credible allele frequency for Gorlin syndrome.
Sources
PM1 p.Gly38 is located in the N-terminal extracellular region of PTCH1 (exon 1), N-terminal to the first transmembrane domain and well outside the sterol-sensing domain (SSD). This position is not in a recognized critical functional domain and is not a statistically significant mutational hotspot per cancerhotspots.org. Details ▾Hide ▴
Evidence considered
- Position 38 is in the N-terminal region
- not in the sterol-sensing domain or any well-characterized critical functional domain. Not a cancerhotspots.org significant residue.
PM2 The variant is present in gnomAD population databases at frequencies inconsistent with absence from controls: v2.1 AF=0.0096% (25/259,610 alleles) and v4.1 AF=0.0125% (200/1,603,018 alleles). While technical AF is below the 0.1% PM2 threshold, 200 alleles in gnomAD v4.1 is not compatible with the PM2 concept of absence from population databases for a rare dominant disorder. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 25 alleles
- gnomAD v4.1: 200 alleles
- gnomAD-Canada: absent. Total AF well below 0.1% threshold but allele count is substantial for a rare dominant disorder.
Sources
PM5 No alternative pathogenic missense variant at the same amino acid residue (p.Gly38) was identified in ClinVar. PM5 criteria require a different amino acid change at the same position that is classified as pathogenic. Details ▾Hide ▴
Evidence considered
- PM5 candidate harvest found no same-residue pathogenic comparators. Unable to confirm classic same-residue PM5 semantics.
Sources
pm5_candidates
PM6 The variant is inherited from the mother, not de novo. Trio WES in PMID:29230040 confirmed maternal transmission. PM6 requires a de novo occurrence with both maternity and paternity confirmed. Details ▾Hide ▴
Evidence considered
- Trio WES confirmed the variant was inherited from the mother
- not de novo.
Sources
PP1 The variant does not cosegregate with disease in the only reported family (PMID:29230040). The variant was transmitted from the mother, who has no cancer history, and the family history is unremarkable for three generations. Details ▾Hide ▴
Evidence considered
- Mother carries variant but is unaffected
- family history unremarkable for 3 generations. No evidence of cosegregation with Gorlin syndrome features.
Sources
PP2 No gene-level missense constraint data was available to establish a low rate of benign missense variation in PTCH1. The variant itself is present in gnomAD, suggesting missense variation at this gene is tolerated in the population. Details ▾Hide ▴
Evidence considered
- No evidence of low benign missense rate in PTCH1. Variant present in gnomAD population databases.
Still missing
- PTCH1 missense Z-score or gnomAD constraint metric not available in evidence brief.
PP3 Multiple in silico predictors uniformly suggest a benign effect: REVEL score 0.162 (below 0.5 threshold), BayesDel score -0.434 (negative), and SpliceAI max delta 0.02 (no predicted splicing impact). PP3 requires pathogenic in silico predictions. Details ▾Hide ▴
Evidence considered
- REVEL=0.162 (benign range)
- BayesDel=-0.434 (benign range)
- SpliceAI max delta=0.02 (no splicing impact).
Sources
PP4 The proband in PMID:29230040 presented with congenital embryonal rhabdomyosarcoma, which can be part of the Gorlin syndrome spectrum. However, the variant-carrying mother is phenotypically unaffected, and the phenotype is not sufficiently specific to support PP4. Details ▾Hide ▴
Evidence considered
- Proband had congenital embryonal RMS
- mother (variant carrier) unaffected. Phenotype not highly specific for Gorlin syndrome.
Sources
PP5 No reputable source has classified this variant as pathogenic. ClinVar reports Likely benign (4 labs), Uncertain significance (2 labs), and Benign (1 lab). PP5 requires a reputable source to have recently reported the variant as pathogenic. Details ▾Hide ▴
Evidence considered
- ClinVar variation 216367: no pathogenic classification from any submitter. Majority classification: Likely benign/benign.
Sources
BA1 gnomAD allele frequency (v2.1: 0.0096%, v4.1: 0.0125%) is well below the BA1 threshold of >1%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.0096%
- gnomAD v4.1 AF=0.0125%. Both << 1% BA1 threshold.
Sources
BS1 gnomAD allele frequency (v2.1: 0.0096%, v4.1: 0.0125%) is below the BS1 threshold of >0.3%. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1 AF=0.0096%
- gnomAD v4.1 AF=0.0125%. Both << 0.3% BS1 threshold.
Sources
BS3 No well-established in vitro or in vivo functional study has demonstrated that p.G38E has no damaging effect on protein function. The available expression data from patient samples (PMID:29230040) is not a controlled functional assay, and in silico benign predictions alone are insufficient for BS3. Details ▾Hide ▴
Evidence considered
- No controlled functional assay demonstrating benign effect. In silico predictors are benign but do not constitute functional evidence per ACMG/AMP.
Still missing
- No well-established functional assay for p.G38E.
Sources
BP1 PTCH1 is a gene in which both missense and truncating variants are established mechanisms of disease for Gorlin syndrome. BP1 applies only when primarily truncating variants cause disease. Details ▾Hide ▴
Evidence considered
- Missense variants in PTCH1 are a known cause of Gorlin syndrome. BP1 not applicable.
BP2 No evidence that this variant has been observed in trans with a known pathogenic PTCH1 variant. BP2 requires observation in trans with a pathogenic variant for a fully penetrant dominant disorder. Details ▾Hide ▴
Evidence considered
- No data on trans configuration with a pathogenic PTCH1 variant.
BP5 The proband in PMID:29230040 also harbored a PTCH2 p.His622Tyr variant, but this was described as a co-occurring/modifier variant, not an alternate molecular basis for the phenotype. BP5 requires a clearly established alternate cause. Details ▾Hide ▴
Evidence considered
- Co-occurring PTCH2 p.His622Tyr described as potential modifier
- not a definitive alternate molecular cause. BP5 not met.
Sources
PS5 No reputable source has recently classified this variant as pathogenic. ClinVar reports Likely benign (4 clinical laboratories), Uncertain significance (2), and Benign (1). Details ▾Hide ▴
Evidence considered
- ClinVar variation ID 216367: Likely benign by 4 labs
- Uncertain significance by 2 labs
- Benign by 1 lab. No expert panel classification.
Sources
Not applicable · 1· recorded as not applicable Show reasons ▾Hide reasons ▴
BP7 N/ANM_000264.5:c.113G>A is a missense variant (p.Gly38Glu), not a synonymous (silent) variant. BP7 is only applicable to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant p.G38E
- BP7 criteria not applicable.
Identifiers
- Gene
- PTCH1
- Transcript
- NM_000264.5
- Coding (HGVS c.)
- NM_000264.5:c.113G>A
- Protein (HGVS p.)
- NP_000255.2:p.(Gly38Glu)
- GRCh38
- chr9:95508249 C>T
- GRCh37
- chr9:98270531 C>T
- ClinVar
- 216367
- COSMIC
- COSV59494982
Gene diagram
Every interpreted variant in PTCH1, mapped onto the exon structure of NM_000264.5. Select a row to find it on the plot.
PTCH1NM_000264.5
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PTCH1
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
200 / 1,603,018 alleles
AF 0.000125 · 0 homozygotes · FAF 0.000384
gnomAD v2.1
25 / 259,610 alleles
AF 9.63e-05 · 0 homozygotes · FAF 9.09e-05
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00012 · 200 / 1,603,018 alleles · 0 hom · FAF 0.00038
| Middle Eastern5 / 5,132 | 0.00097 |
| European (non-Finnish)167 / 1,176,580 | 0.00014 |
| East Asian5 / 44,424 | 0.00011 |
| South Asian10 / 90,372 | 0.00011 |
| Remaining individuals5 / 61,874 | 8.1e-05 |
| African/African American4 / 74,572 | 5.4e-05 |
| Admixed American2 / 59,520 | 3.4e-05 |
| European (Finnish)2 / 60,190 | 3.3e-05 |
0 alternate alleles recorded in 2 other groups: Amish, Ashkenazi Jewish.
gnomAD v2.1
AF 9.6e-05 · 25 / 259,610 alleles · 0 hom · FAF 9.1e-05
| European (non-Finnish)19 / 117,370 | 0.00016 |
| South Asian2 / 29,594 | 6.8e-05 |
| Admixed American2 / 34,172 | 5.9e-05 |
| East Asian1 / 18,584 | 5.4e-05 |
| African/African American1 / 22,176 | 4.5e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, European (Finnish), Remaining individuals.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000124765; MAF= 0.01248%, 200/1603018 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000974279; MAF= 0.09743%, 5/5132 alleles, homozygotes = 0); grpmax FAF= 0.00038378.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.62983e-05; MAF= 0.00963%, 25/259610 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000161881; MAF= 0.01619%, 19/117370 alleles, homozygotes = 0); grpmax FAF= 9.09e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0003266906239790918, 6/18366 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.162
- BayesDel
- -0.434
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on gene product: REVEL score 0.162 (benign range, below 0.5 threshold), BayesDel score -0.434 (negative, predicting benign), and SpliceAI max delta score 0.02 (no predicted splicing impact). Details ▾Hide ▴
Evidence considered
- REVEL=0.162 (benign)
- BayesDel=-0.434 (benign)
- SpliceAI max delta=0.02 (no splicing impact). Multiple concordant in silico predictions of benign effect.
Sources
PP3 Multiple in silico predictors uniformly suggest a benign effect: REVEL score 0.162 (below 0.5 threshold), BayesDel score -0.434 (negative), and SpliceAI max delta 0.02 (no predicted splicing impact). PP3 requires pathogenic in silico predictions. Details ▾Hide ▴
Evidence considered
- REVEL=0.162 (benign range)
- BayesDel=-0.434 (benign range)
- SpliceAI max delta=0.02 (no splicing impact).
Sources
BP7 N/ANM_000264.5:c.113G>A is a missense variant (p.Gly38Glu), not a synonymous (silent) variant. BP7 is only applicable to synonymous variants with no predicted splice impact. Details ▾Hide ▴
Evidence considered
- Missense variant p.G38E
- BP7 criteria not applicable.
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.162. BayesDel score = -0.434182.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.
Recorded publications
-
PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.Richards S et al. · 2015ACMG/AMP standards and guidelines for the interpretation of sequence variants. This is a methodological framework document that defines variant classification criteria. It does not discuss PTCH1 or the specific variant NM_000264.5:c.113G>A.Does not name this variant
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.Describes a standardized DNA variant scoring system for Mendelian disorders. This methodology paper does not discuss PTCH1 or NM_000264.5:c.113G>A specifically.Does not name this variant
-
PMID 29230040 ↗Congenital embryonal rhabdomyosarcoma caused by heterozygous concomitant PTCH1 and PTCH2 germline mutations.Taeubner J et al. · 2018Heterozygous PTCH1 p.(Gly38Glu) was identified by trio WES in a newborn with congenital embryonal rhabdomyosarcoma, co-occurring with a PTCH2 p.(His622Tyr) variant. The PTCH1 variant was inherited from the mother, who has no cancer history and an unremarkable three-generation family history. qRT-PCR showed decreased PTCH1 expression and increased GLI1 in patient samples, but no controlled functional assay of the variant was performed. The authors speculate PTCH2 modulates tumorigenesis linked to the PTCH1 variant.Names this variant
Quoted passage
The PTCH1 mutation p.(Gly38Glu) is inherited from the mother, whereas the PTCH2 p.(His622Tyr) mutation is transmitted from the father.
Abstract, line 28; Results, lines 217-218, 252-255; Figure 2; Discussion, lines 298-304
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004National Society of Genetic Counselors recommendations for cancer genetic risk assessment and counseling. General guideline document that does not discuss specific PTCH1 variants.Does not name this variant
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PMID 21304560 ↗Clinical utility gene card for: Gorlin syndrome.Lo Muzio L et al. · 2011Clinical utility gene card for Gorlin syndrome. Gene-level review of PTCH1-associated disease; does not discuss the specific variant NM_000264.5:c.113G>A.Does not name this variant
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015ACMG/NSGC practice guideline for cancer predisposition referral indications. Includes Gorlin syndrome (NBCCS) in its referral criteria tables but does not discuss specific PTCH1 variants.Does not name this variant
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PMID 26389258 ↗Cancer Genetics Risk Assessment and Counseling (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ Cancer Genetics Risk Assessment and Counseling summary. General cancer genetics resource that does not discuss specific PTCH1 variants.Does not name this variant
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PMID 26389333 ↗Genetics of Skin Cancer (PDQ®): Health Professional Version.PDQ Cancer Genetics Editorial Board · 2002PDQ Genetics of Skin Cancer summary. Includes discussion of Gorlin syndrome and PTCH1 at the gene level but does not mention the specific variant NM_000264.5:c.113G>A.Does not name this variant
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Nykamp K et al. · 2017Sherloc variant classification framework paper. Methodological refinement of ACMG-AMP criteria; does not discuss PTCH1 or NM_000264.5:c.113G>A.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
200 / 1,603,018 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.020
Open source ↗
ClinVar
4 Likely benign · 2 Uncertain significance · 1 Benign
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/216367/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/9-98270531-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr9-95508249-C-T?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/9-95508249-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000264.5%3Ac.113G…
- OncoKB ↗www.oncokb.org/gene/PTCH1/G38E
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=127883185
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000124765; MAF= 0.01248%, 200/1603018 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000974279; MAF= 0.09743%, 5/5132 alleles, homozygotes = 0); grpmax FAF= 0.00038378.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 9.62983e-05; MAF= 0.00963%, 25/259610 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 0.000161881; MAF= 0.01619%, 19/117370 alleles, homozygotes = 0); grpmax FAF= 9.09e-05.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.0003266906239790918, 6/18366 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (4 clinical laboratories) and as Uncertain significance (2 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 216367)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02). REVEL score = 0.162. BayesDel score = -0.434182.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PTCH1, a tumor suppressor and inhibitor of the hedgehog pathway, is recurrently mutated in basal cell carcinoma.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV59494982, n = 3 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.