About PMS2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PMS2 c.86G>C, p.(Gly29Ala)
Classification
Not classified
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. Select a step to read what it means.
Not classified yet.Select a step to read what it means.
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 ClinGen PMS2 VCEP v2.0.0. 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: 1
Benign evidence criteria: 1
Pathogenic criteria applied · 1
PP3Moderate
PP3 · moderate
The HCI MAPP/PP2 Prior P score for p.Gly29Ala (PMS2_00179) is 0.8883, which exceeds the VCEP PP3_Moderate threshold of >0.81. This in silico prior probability supports a pathogenic computational prediction.
Benign criteria applied · 1
BS1Strong
BS1 · strong
Per VCEP PMS2 rule, BS1_Strong applies when gnomAD v4 grpmax filtering allele frequency is ≥ 0.00028 (0.028%) and < 0.0028 (0.28%), and the variant is excluded as a founder pathogenic variant. The grpmax FAF for this variant is 0.00037135 (0.037%), which falls within this range. The variant is observed across multiple populations with highest frequency in Ashkenazi Jewish (0.699%), but there is no definitive evidence of founder pathogenic status. One homozygote is observed in gnomAD v4, further supporting that this variant is unlikely to be highly penetrant.
Recorded classification: Not classified
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PMS2 Version 2.0.0 v2.0.0 criteria-combination framework: matched Rule22 (Benign.Strong >=1 + Pathogenic.Moderate >=1) with applied criteria: PP3 moderate, BS1 strong; maps to Uncertain Significance - Conflicting Evidence.
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
808 / 1,610,736 alleles
gnomAD v4.1: 808 / 1,610,736 alleles. Recorded AF 0.000501634. Recorded homozygote count 1.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000602527; MAF= 0.06025%, 167/277166 alleles, homozygotes = 1) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00664192; MAF= 0.66419%, 68/10238 alleles, homozygotes = 0); grpmax FAF= 0.00040995.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000488599348534202, 9/18420 alleles, homozygotes = 0).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
19 reported laboratory submissions
10 Likely benign · 5 Uncertain significance · 2 Benign · 1 Likely Benign · 1 Uncertain Significance. ClinVar API review status: criteria provided, conflicting classifications.
Context only
ClinVar ↗
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. PMS2, an endonuclease involved in DNA repair, is altered in various cancers.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PMS2 VCEP v2.0.0, with the data and sources behind each one.
27 criteria with recorded statuses: 2 met · 13 not met · 0 not assessed · 12 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000535.7:c.86G>C (p.Gly29Ala) is a missense variant in exon 2 of PMS2, a gene in which loss-of-function is an established mechanism for Lynch syndrome.
This variant is present in gnomAD v4.1 at an allele frequency of 0.050% (808/1,610,736 alleles, grpmax FAF=0.037%), which meets the VCEP PMS2 BS1_Strong threshold (grpmax FAF ≥ 0.028% and < 0.28%). One homozygote is observed in both gnomAD v2 and v4, further supporting that this variant is unlikely to be highly penetrant.
The HCI MAPP/PP2 Prior P score of 0.8883 exceeds the VCEP PP3_Moderate threshold (>0.81), providing in silico evidence for a deleterious effect.
This variant is reported in ClinVar as Likely benign by 10 clinical laboratories and as Benign by 2 laboratories, though 5 laboratories classify it as Uncertain significance. The overall ClinVar classification is Likely benign with review status of criteria provided, single submitter.
SpliceAI predicts no splicing impact (max delta score 0.00), and the variant does not lie in a statistically significant mutational hotspot.
No functional studies, segregation data, tumor phenotype data, or de novo observations are available for this variant. No peer-reviewed publication specifically mentions NM_000535.7:c.86G>C.
No criteria match.
Met · 2
PP3 ModerateThe HCI MAPP/PP2 Prior P score for p.Gly29Ala (PMS2_00179) is 0.8883, which exceeds the VCEP PP3_Moderate threshold of >0.81. This in silico prior probability supports a pathogenic computational prediction. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.8883 (MAPP score 22.05
- custom PP2 score 0.998). Exceeds VCEP PP3_Moderate threshold (>0.81).
Sources
hci_priorcspec ↗
BS1 StrongPer VCEP PMS2 rule, BS1_Strong applies when gnomAD v4 grpmax filtering allele frequency is ≥ 0.00028 (0.028%) and < 0.0028 (0.28%), and the variant is excluded as a founder pathogenic variant. The grpmax FAF for this variant is 0.00037135 (0.037%), which falls within this range. The variant is observed across multiple populations with highest frequency in Ashkenazi Jewish (0.699%), but there is no definitive evidence of founder pathogenic status. One homozygote is observed in gnomAD v4, further supporting that this variant is unlikely to be highly penetrant. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 0.00037135 (between 0.00028 and 0.0028 VCEP BS1 range). 808 alleles observed
- including 1 homozygote. Highest subpopulation frequency in Ashkenazi Jewish (AF=0.00699).
Sources
Not met · 13 · evaluated, threshold not reached
PS1 PS1 requires a different nucleotide change producing the same amino acid change (p.Gly29Ala) that has been classified as Pathogenic or Likely Pathogenic by this VCEP. No such comparator variant exists; c.86G>C is the only nucleotide change producing p.Gly29Ala in the PMS2 HCI priors database. Details ▾Hide ▴
Evidence considered
- HCI-PRIORS-PMS2.txt confirms c.86G>C is the sole nucleotide substitution encoding p.Gly29Ala at this codon.
Sources
hci_prior
PS2 No de novo observations have been reported for NM_000535.7:c.86G>C in any available data source. PS2 requires documented de novo occurrence with confirmed maternity and paternity in a patient with an MMR-deficient LS-spectrum tumor. Details ▾Hide ▴
Evidence considered
- No de novo evidence identified in ClinVar
- literature
- or case data.
Still missing
- No de novo reports available for this variant.
PS3 No variant-specific functional assay data exist for NM_000535.7:c.86G>C (p.Gly29Ala). The ClinGen InSiGHT functional assay SVI documentation lists calibrated CIMRA, chemical selection, CRISPR, and cDNA-based assays, but none have tested this variant. OncoKB classifies this variant as Unknown Oncogenic Effect with no curated functional evidence. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet documents approved assays (CIMRA
- chemical selection
- cDNA analysis) but this variant has not been tested in any of them. OncoKB reports no variant-specific functional evidence.
Still missing
- No functional assay data available for this variant.
Sources
oncokb ↗vcep_functional_assay_svi_documentation_mmr
PM2 Per VCEP PMS2 rule, PM2_Supporting requires absence or extremely rare allele frequency <0.00002 (<1 in 50,000 alleles) in gnomAD v4. This variant is present in gnomAD v4 at AF=0.0005016 (808/1,610,736 alleles, grpmax FAF=0.00037135), which is approximately 25-fold above the PM2 threshold. PM2 is not met. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 808 alleles
- AF=0.0005016
- grpmax FAF=0.00037135
- well above the VCEP PM2_Supporting threshold of <0.00002.
Sources
PM5 PM5 requires a different missense change at amino acid residue Gly29 classified as Pathogenic or Likely Pathogenic by this VCEP. The VCEP pilot variants spreadsheet contains no PMS2 missense variants at codon 29. No same-residue comparator with a VCEP P/LP classification exists. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json returned zero candidates. VCEP pilot variants spreadsheet lists no PMS2 codon 29 missense variants with P/LP classification.
Sources
PP1 No co-segregation data are available for NM_000535.7:c.86G>C. PP1 requires co-segregation with disease in pedigrees with a combined Bayes Likelihood Ratio meeting VCEP thresholds. Details ▾Hide ▴
Evidence considered
- No segregation data available in ClinVar submissions
- literature
- or case materials.
Still missing
- No pedigree or co-segregation data available.
PP4 No tumor MSI/IHC data are available for NM_000535.7:c.86G>C carriers. PP4 requires MSI-H colorectal/endometrial tumors with MMR protein expression loss consistent with variant location. Details ▾Hide ▴
Evidence considered
- No tumor phenotype data (MSI status
- IHC) available from any source.
Still missing
- No tumor MSI/IHC data available for carriers of this variant.
BA1 Per VCEP PMS2 rule, BA1 requires gnomAD v4 grpmax filtering allele frequency ≥ 0.0028 (0.28%). This variant has grpmax FAF = 0.00037135 (0.037%), which is approximately 7.5-fold below the BA1 threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 0.00037135
- below VCEP BA1 threshold of ≥0.0028.
Sources
BS2 No evidence of co-occurrence in trans with a known pathogenic PMS2 variant in a patient with colorectal cancer after age 45 without CMMRD features. BS2 requires confirmed phase with a pathogenic variant and specific clinical presentation. Details ▾Hide ▴
Evidence considered
- No co-occurrence or phase data available.
Still missing
- No data on in trans co-occurrence with pathogenic PMS2 variants.
BS3 No functional assay data demonstrating normal MMR function for NM_000535.7:c.86G>C exist. The VCEP functional assay documentation defines calibrated assays (CIMRA, chemical selection, cDNA analysis) but this variant has not been tested in any of them. Details ▾Hide ▴
Evidence considered
- No variant-specific functional evidence for benign effect. OncoKB reports Unknown Oncogenic Effect.
Still missing
- No functional data demonstrating normal/proficient MMR function.
Sources
vcep_functional_assay_svi_documentation_mmroncokb ↗
BS4 No co-segregation data are available to demonstrate lack of segregation with disease. BS4 requires a combined Bayes Likelihood Ratio meeting VCEP thresholds from pedigrees. Details ▾Hide ▴
Evidence considered
- No segregation or lack-of-segregation data available.
Still missing
- No pedigree co-segregation data.
BP4 Per VCEP PMS2 rule, BP4_Supporting requires an HCI MAPP/PP2 Prior P score <0.11. The HCI prior for p.Gly29Ala is 0.8883, which is far above the benign threshold and instead supports pathogenicity (PP3_Moderate). Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.8883
- well above BP4_Supporting threshold of <0.11.
Sources
hci_priorcspec ↗
BP5 No tumor data (MSS status, MMR protein expression) are available for carriers of this variant. BP5 requires CRC/endometrial tumors with MSS and/or no loss of MMR protein expression or LS spectrum tumors with inconsistent protein loss. Details ▾Hide ▴
Evidence considered
- No tumor phenotype data available.
Still missing
- No tumor MSS/IHC data for carriers.
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to this missense variant (c.86G>C, p.Gly29Ala). The ClinGen InSiGHT PMS2 VCEP v2.0.0 restricts PVS1 to null variants: nonsense/frameshift introducing PTC ≤ codon 798, canonical ±1,2 splice variants, initiation codon variants, and large genomic alterations. Details ▾Hide ▴
Evidence considered
- Missense substitution does not meet any VCEP PVS1 criterion bucket. Variant class is missense
- not null.
Sources
cspec ↗pvs1_variant_assessment
PS4 VCEPPS4 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
PM1 VCEPPM1 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
PM6 VCEPPM6 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
PP2 VCEPPP2 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
PP5 VCEPPP5 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
BP1 VCEPBP1 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
BP2 VCEPBP2 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
BP3 VCEPBP3 applies to in-frame deletions/insertions in repetitive regions without a known function. This is a single-nucleotide missense substitution. Details ▾Hide ▴
Evidence considered
- Variant is a substitution
- not an in-frame indel in a repetitive region.
BP6 VCEPBP6 is marked Not Applicable by the ClinGen InSiGHT PMS2 VCEP v2.0.0. Details ▾Hide ▴
BP7 N/ABP7 applies to synonymous (silent) or intronic variants at or beyond -21/+7. NM_000535.7:c.86G>C is a missense variant producing p.Gly29Ala and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense variant
- does not meet BP7 criteria for synonymous/intronic variants.
Sources
PS5 N/APS5 is not defined in the ClinGen InSiGHT PMS2 VCEP v2.0.0 criteria set. The VCEP framework does not include PS5 among its specified criteria. Details ▾Hide ▴
Identifiers
- Gene
- PMS2
- Transcript
- NM_000535.7
- Coding (HGVS c.)
- NM_000535.7:c.86G>C
- Protein (HGVS p.)
- NP_000526.2:p.(Gly29Ala)
- GRCh38
- chr7:6005969 C>G
- GRCh37
- chr7:6045600 C>G
- ClinVar
- 1207170, 41721
Gene diagram
Every interpreted variant in PMS2, mapped onto the exon structure of NM_000535.7. Select a row to find it on the plot.
PMS2NM_000535.7
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 PMS2
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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
808 / 1,610,736 alleles
AF 0.000502 · 1 homozygotes · FAF 0.000371
gnomAD v2.1
167 / 277,166 alleles
AF 0.000603 · 1 homozygotes · FAF 0.00041
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.0005 · 808 / 1,610,736 alleles · 1 hom · FAF 0.00037
| Ashkenazi Jewish207 / 29,596 | 0.007 |
| Remaining individuals57 / 62,304 | 0.00091 |
| European (Finnish)31 / 62,910 | 0.00049 |
| European (non-Finnish)474 / 1,179,808 | 0.00041 hom |
| South Asian29 / 90,982 | 0.00032 |
| Admixed American5 / 59,984 | 8.3e-05 |
| African/African American5 / 74,948 | 6.7e-05 |
0 alternate alleles recorded in 3 other groups: Amish, East Asian, Middle Eastern.
gnomAD v2.1
AF 0.0006 · 167 / 277,166 alleles · 1 hom · FAF 0.00041
| Ashkenazi Jewish68 / 10,238 | 0.0066 |
| Remaining individuals6 / 7,152 | 0.00084 |
| European (Finnish)14 / 25,110 | 0.00056 |
| European (non-Finnish)67 / 125,388 | 0.000531 hom |
| South Asian8 / 30,376 | 0.00026 |
| Admixed American3 / 35,324 | 8.5e-05 |
| African/African American1 / 23,752 | 4.2e-05 |
0 alternate alleles recorded in 1 other group: East Asian.
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000501634; MAF= 0.05016%, 808/1610736 alleles, homozygotes = 1) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00699419; MAF= 0.69942%, 207/29596 alleles, homozygotes = 0); grpmax FAF= 0.00037135.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000602527; MAF= 0.06025%, 167/277166 alleles, homozygotes = 1) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00664192; MAF= 0.66419%, 68/10238 alleles, homozygotes = 0); grpmax FAF= 0.00040995.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000488599348534202, 9/18420 alleles, homozygotes = 0).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.825
- BayesDel
- 0.346
How the predictions were used
PP3 ModerateThe HCI MAPP/PP2 Prior P score for p.Gly29Ala (PMS2_00179) is 0.8883, which exceeds the VCEP PP3_Moderate threshold of >0.81. This in silico prior probability supports a pathogenic computational prediction. Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.8883 (MAPP score 22.05
- custom PP2 score 0.998). Exceeds VCEP PP3_Moderate threshold (>0.81).
Sources
hci_priorcspec ↗
BP4 Per VCEP PMS2 rule, BP4_Supporting requires an HCI MAPP/PP2 Prior P score <0.11. The HCI prior for p.Gly29Ala is 0.8883, which is far above the benign threshold and instead supports pathogenicity (PP3_Moderate). Details ▾Hide ▴
Evidence considered
- HCI prior probability = 0.8883
- well above BP4_Supporting threshold of <0.11.
Sources
hci_priorcspec ↗
BP7 N/ABP7 applies to synonymous (silent) or intronic variants at or beyond -21/+7. NM_000535.7:c.86G>C is a missense variant producing p.Gly29Ala and does not qualify. Details ▾Hide ▴
Evidence considered
- Missense variant
- does not meet BP7 criteria for synonymous/intronic variants.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.825. BayesDel score = 0.346178. HCI prior probability for pathogenicity = 0.8883. MAPP score = 22.05. Custom PP2 score = 0.998.
9 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
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PMID 25070057 ↗Guidelines on genetic evaluation and management of Lynch syndrome: a consensus statement by the US Multi-society Task Force on colorectal cancer.Multi-Society Task Force consensus guidelines on genetic evaluation and management of Lynch syndrome. Discusses PMS2-associated cancer risks at the gene level but does not mention any specific PMS2 variant.Does not name this variant
-
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.ACMG/AMP standards and guidelines for sequence variant interpretation. Provides the generic classification framework but does not discuss NM_000535.7:c.86G>C or any specific PMS2 variant.Does not name this variant
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PMID 26898890 ↗Prioritizing Variants in Complete Hereditary Breast and Ovarian Cancer Genes in Patients Lacking Known BRCA Mutations.Caminsky NG et al. · 2016Study of 20 hereditary breast and ovarian cancer genes in 287 patients lacking BRCA mutations. PMS2 was sequenced but no specific PMS2 variant results are reported. NM_000535.7:c.86G>C was not identified in this paper.Does not name this variant
-
PMID 28135145 ↗Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.Yurgelun MB et al. · 2017Study of cancer susceptibility gene mutations in individuals with colorectal cancer. Abstract mentions PMS2 as one of the genes analyzed but does not name specific variants.Does not name this variant
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PMID 31391288 ↗Tumour characteristics provide evidence for germline mismatch repair missense variant pathogenicity.Study quantifying tumor MSI/IHC characteristics to assess germline MMR missense variant pathogenicity among 4,740 patients. Models tumor characteristic likelihood ratios but does not list individual variant results for NM_000535.7:c.86G>C.Does not name this variant
-
PMID 34284872 ↗Mutational profile of hereditary breast and ovarian cancer - Establishing genetic testing guidelines in a developing country.Full-text download retrieved an unrelated publication (philosophy text on 'Confim') rather than the intended hereditary breast/ovarian cancer study. The correct paper about mutational profiles in Serbia could not be reviewed.Does not name this variant
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.National Society of Genetic Counselors practice recommendations for cancer genetic risk assessment and counseling. Provides general guidance on hereditary cancer counseling but does not discuss specific variants.Does not name this variant
-
PMID 20301390 ↗Lynch Syndrome.GeneReviews clinical summary of Lynch syndrome. Provides gene-level overview of PMS2-associated cancer risks and management but does not discuss individual variants.Does not name this variant
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Sherloc refinement of ACMG-AMP variant classification criteria. Provides variant classification methodology but does not discuss NM_000535.7:c.86G>C.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
808 / 1,610,736 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
10 Likely benign · 5 Uncertain significance · 2 Benign · 1 Likely Benign · 1 Uncertain Significance
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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1578297058
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/41721/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/7-6045600-C-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr7-6005969-C-G?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/7-6005969-C-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000535.7%3Ac.86G%…
- OncoKB ↗www.oncokb.org/gene/PMS2/G29A
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=PMS2+c.86G%3EC
- 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= 0.000501634; MAF= 0.05016%, 808/1610736 alleles, homozygotes = 1) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00699419; MAF= 0.69942%, 207/29596 alleles, homozygotes = 0); grpmax FAF= 0.00037135.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.000602527; MAF= 0.06025%, 167/277166 alleles, homozygotes = 1) and has highest observed frequency in the Ashkenazi Jewish population (AF= 0.00664192; MAF= 0.66419%, 68/10238 alleles, homozygotes = 0); grpmax FAF= 0.00040995.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000488599348534202, 9/18420 alleles, homozygotes = 0).
ClinVar
This variant has been reported in ClinVar as Likely benign (10 clinical laboratories) and as Uncertain significance (5 clinical laboratories) and as Benign (2 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 41721)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.825. BayesDel score = 0.346178. HCI prior probability for pathogenicity = 0.8883. MAPP score = 22.05. Custom PP2 score = 0.998.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PMS2, an endonuclease involved in DNA repair, is altered in various cancers.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.