About PMS2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PMS2 c.241G>A, p.(Glu81Lys)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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: 0
Benign evidence criteria: 1
Pathogenic criteria applied · 0
No pathogenic criterion marked as applied in the recorded assessment.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
For PMS2 missense variants, the VCEP prioritizes the HCI prior. This variant has an HCI prior probability of 0.0446, which is below the BP4 threshold of <0.11, supporting benign computational evidence. SpliceAI also predicts no splice impact with a max delta score of 0.00.
Recorded classification: Uncertain significance
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 was evaluated deterministically with applied criteria: BP4 supporting; no rule matched the adjudicated criteria.
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
52 / 1,593,986 alleles
gnomAD v4.1: 52 / 1,593,986 alleles. Recorded AF 3.26226e-05. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59477e-05; MAF= 0.00159%, 4/250820 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00016372; MAF= 0.01637%, 1/6108 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000108601; MAF= 0.01086%, 2/18416 alleles, homozygotes = 0) and has highest observed frequency in the amr population (AF= 0.00238663; grpmax FAF95= 0.00042326).
No listed criterion applied
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
15 reported laboratory submissions
13 Uncertain significance · 1 Benign · 1 Uncertain Significance.
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
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV56222918, n = 1 times).
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.
28 criteria with recorded statuses: 1 met · 7 not met · 9 not assessed · 11 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
The PMS2 c.241G>A (p.Glu81Lys, p.E81K) variant has been reported in ClinVar predominantly as a variant of uncertain significance, with one benign submission and no expert panel classification.
This variant is present in population databases, including gnomAD v4.1 at AF 0.0000326 (52/1,593,986 alleles) and gnomAD v2.1 at AF 0.0000159 (4/250,820 alleles); the gnomAD v4.1 frequency is above the PMS2 PM2 threshold of <0.00002 and below the BS1 and BA1 thresholds.
For PMS2 missense variants, the HCI prior is the primary computational metric; this variant has an HCI prior probability of 0.0446, which is below the BP4 threshold of <0.11 and supports BP4_Supporting, while SpliceAI predicts no splice impact with a max delta score of 0.00.
No criteria match.
Met · 1
BP4 SupportingFor PMS2 missense variants, the VCEP prioritizes the HCI prior. This variant has an HCI prior probability of 0.0446, which is below the BP4 threshold of <0.11, supporting benign computational evidence. SpliceAI also predicts no splice impact with a max delta score of 0.00. Details ▾Hide ▴
Rule
For PMS2 missense variants, BP4_Supporting is met when the HCI prior probability is <0.11.
Evidence considered
- HCI prior probability 0.0446
- SpliceAI max delta score 0.00
- REVEL 0.516
- BayesDel 0.0236541
Sources
Not met · 7 · evaluated, threshold not reached
PVS1 This variant is a missense substitution, p.(Glu81Lys), and does not fall into the PMS2 VCEP loss-of-function categories for PVS1. Details ▾Hide ▴
Rule
PMS2 VCEP PVS1 is reserved for qualifying loss-of-function or proven splice-aberrant variants.
Evidence considered
- PMS2 VCEP PVS1 framework applies to null or proven splice-aberrant variants
- p.(Glu81Lys) is a missense change
Sources
PS1 No evidence was identified that a different nucleotide change causing the same p.(Glu81Lys) amino acid substitution has already been established by the PMS2 VCEP as Pathogenic or Likely Pathogenic. Details ▾Hide ▴
Rule
PMS2 VCEP PS1 requires a different nucleotide change causing the same amino acid substitution already established by the VCEP.
Evidence considered
- PMS2 VCEP PS1 same-amino-acid rule reviewed
- ClinVar exact-variant record reviewed
Still missing
- A confirmed same-amino-acid comparator established by the PMS2 VCEP would be needed.
Sources
PM2 This variant is present in gnomAD v4.1 at AF 0.0000326 (52/1,593,986 alleles), which is above the PMS2 PM2 threshold of <0.00002, so PM2_Supporting is not met. Details ▾Hide ▴
Rule
PMS2 VCEP PM2_Supporting requires allele frequency <0.00002 in gnomAD v4.
Evidence considered
- gnomAD v4.1 total AF 0.0000326
- PMS2 VCEP PM2 threshold <0.00002
Sources
PM5 No qualifying same-residue pathogenic or likely pathogenic missense comparator was identified for codon 81, and this variant also lacks the PP3 support required before applying PMS2 PM5. Details ▾Hide ▴
Rule
PMS2 VCEP PM5 requires a qualifying same-residue missense comparator and PP3 support for the queried missense variant.
Evidence considered
- PM5 candidate harvest found no usable same-residue comparators
- PP3 support is not present because HCI prior is below the PMS2 PP3 threshold
Still missing
- A same-residue PMS2 missense comparator established at the protein level by the governing framework
Sources
PP3 For PMS2 missense variants, the VCEP prioritizes the HCI prior. This variant has an HCI prior probability of 0.0446, which is below the PP3 thresholds of >0.68 for Supporting and >0.81 for Moderate, so PP3 is not met. SpliceAI also predicts no splice impact with a max delta score of 0.00. Details ▾Hide ▴
Rule
For PMS2 missense variants, PP3 requires HCI prior >0.68 (Supporting) or >0.81 (Moderate).
Evidence considered
- HCI prior probability 0.0446
- SpliceAI max delta score 0.00
- REVEL 0.516
- BayesDel 0.0236541
Sources
BA1 The gnomAD v4.1 grpmax filtering allele frequency is 0.0000901, which is below the PMS2 BA1 threshold of 0.0028, so BA1 is not met. Details ▾Hide ▴
Rule
PMS2 VCEP BA1 requires gnomAD v4 grpmax filtering allele frequency ≥0.0028.
Evidence considered
- gnomAD v4.1 grpmax FAF 0.0000901
- PMS2 VCEP BA1 threshold 0.0028
Sources
BS1 The gnomAD v4.1 highest observed population frequency is 0.000225 and the grpmax filtering allele frequency is 0.0000901, both below the PMS2 BS1 threshold of 0.00028, so BS1 is not met. Details ▾Hide ▴
Rule
PMS2 VCEP BS1 requires gnomAD v4 grpmax filtering allele frequency ≥0.00028 and <0.0028.
Evidence considered
- Highest observed population AF 0.000225 in gnomAD v4.1
- gnomAD v4.1 grpmax FAF 0.0000901
- PMS2 VCEP BS1 threshold 0.00028
Sources
Not assessed · 9 · no assessment recorded
PS2 No confirmed de novo occurrence with the tumor and parental-testing requirements needed for PMS2 PS2 was identified. Details ▾Hide ▴
Rule
PMS2 VCEP PS2 uses a de novo point system tied to confirmed parentage and tumor context.
Evidence considered
- PMS2 VCEP de novo point system reviewed
- ClinVar exact-variant record did not provide usable de novo evidence
Still missing
- Confirmed maternity and paternity data
- Tumor evidence consistent with the PMS2-associated MMR pattern
Sources
PS3 No validated PMS2 functional assay result for p.(Glu81Lys) was identified that would support a damaging effect under the PMS2 VCEP functional framework. Details ▾Hide ▴
Rule
PMS2 VCEP PS3 requires qualifying calibrated or framework-compatible abnormal functional evidence.
Evidence considered
- PMS2 VCEP functional assay framework reviewed
- ClinVar exact-variant record did not provide extractable variant-specific functional evidence
Still missing
- Variant-specific validated functional assay data
Sources
PM3 No phase-confirmed observation of this variant in trans with a pathogenic PMS2 variant in a constitutional mismatch repair deficiency context was identified. Details ▾Hide ▴
Rule
PMS2 VCEP PM3 uses a point-based framework for trans observations in the appropriate recessive disease setting.
Evidence considered
- PMS2 VCEP PM3 point system reviewed
- No usable trans/CMMRD evidence identified in ClinVar exact-variant materials
Still missing
- Confirmed trans observation with a pathogenic PMS2 variant
- Clinical context meeting the PMS2 PM3 point system
Sources
PP1 No informative segregation data were identified for this variant, so the PMS2 PP1 Bayes likelihood ratio thresholds cannot be evaluated. Details ▾Hide ▴
Rule
PMS2 VCEP PP1 requires segregation data meeting Bayes likelihood ratio thresholds.
Evidence considered
- PMS2 VCEP segregation thresholds reviewed
- No usable segregation details identified in exact-variant ClinVar materials
Still missing
- Pedigree-based segregation data with a calculable Bayes likelihood ratio
Sources
PP4 No tumor microsatellite instability or immunohistochemistry evidence was identified to determine whether the clinical and tumor features meet the PMS2 PP4 thresholds. Details ▾Hide ▴
Rule
PMS2 VCEP PP4 depends on qualifying MSI-H and/or MMR protein-expression evidence.
Evidence considered
- PMS2 VCEP PP4 tumor-based thresholds reviewed
Still missing
- MSI and/or MMR immunohistochemistry results
- Number of independent informative tumors and families
Sources
BS2 No confirmed in-trans co-occurrence with a known pathogenic PMS2 variant in an individual meeting the PMS2 BS2 clinical requirements was identified. Details ▾Hide ▴
Rule
PMS2 VCEP BS2 requires qualifying in-trans co-occurrence and clinical context inconsistent with CMMRD.
Evidence considered
- PMS2 VCEP BS2 co-occurrence rule reviewed
Still missing
- Confirmed phase with a pathogenic PMS2 variant
- Clinical data excluding constitutional mismatch repair deficiency features
Sources
BS3 No validated variant-specific functional study was identified showing retained PMS2 function or normal RNA behavior that would support BS3. Details ▾Hide ▴
Rule
PMS2 VCEP BS3 requires qualifying normal-function evidence from accepted functional or RNA assays.
Evidence considered
- PMS2 VCEP benign functional framework reviewed
- ClinVar exact-variant record did not provide extractable benign functional evidence
Still missing
- Variant-specific benign functional or RNA evidence
Sources
BS4 No informative family data were identified to show lack of segregation with disease, so BS4 cannot be evaluated. Details ▾Hide ▴
Rule
PMS2 VCEP BS4 requires lack of segregation meeting Bayes likelihood ratio thresholds.
Evidence considered
- PMS2 VCEP BS4 segregation thresholds reviewed
- No usable non-segregation data identified in exact-variant ClinVar materials
Still missing
- Pedigree-based non-segregation data with a calculable Bayes likelihood ratio
Sources
BP5 No tumor phenotype data were identified to determine whether observed tumor features are inconsistent with a germline PMS2 explanation under the PMS2 BP5 rule. Details ▾Hide ▴
Rule
PMS2 VCEP BP5 depends on qualifying tumor features inconsistent with the gene under review.
Evidence considered
- PMS2 VCEP BP5 tumor-based rule reviewed
Still missing
- Tumor MSI/IHC and related somatic-context details
Sources
Not applicable · 11· recorded as not applicable Show reasons ▾Hide reasons ▴
PS4 VCEPPS4 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
PM1 VCEPPM1 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
PM4 VCEPPM4 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
PM6 VCEPPM6 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
PP2 VCEPPP2 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
PP5 VCEPPP5 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
BP1 VCEPBP1 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
BP2 VCEPBP2 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
BP3 VCEPBP3 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
BP6 VCEPBP6 is marked not applicable in the PMS2 VCEP framework. Details ▾Hide ▴
BP7 N/AThis variant is a missense substitution rather than a synonymous or qualifying intronic change, so BP7 does not apply. Details ▾Hide ▴
Evidence considered
- p.(Glu81Lys) is a missense variant
- PMS2 VCEP BP7 is for synonymous or qualifying intronic variants
Sources
Identifiers
- Gene
- PMS2
- Transcript
- NM_000535.7
- Coding (HGVS c.)
- NM_000535.7:c.241G>A
- Protein (HGVS p.)
- NP_000526.2:p.(Glu81Lys)
- GRCh38
- chr7:6003981 C>T
- GRCh37
- chr7:6043612 C>T
- ClinVar
- 3308111, 1748563, 182817
- COSMIC
- COSV56222918
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
52 / 1,593,986 alleles
AF 3.26e-05 · 0 homozygotes · FAF 9.01e-05
gnomAD v2.1
4 / 250,820 alleles
AF 1.59e-05 · 0 homozygotes · FAF 2.93e-06
gnomAD-Canada v1.0
2 / 18,416 alleles
AF 0.000109 · 0 homozygotes · FAF 0.000423
By genetic ancestry
gnomAD v4.1
AF 3.3e-05 · 52 / 1,593,986 alleles · 0 hom · FAF 9e-05
| Middle Eastern1 / 4,440 | 0.00023 |
| Admixed American10 / 59,928 | 0.00017 |
| East Asian2 / 44,782 | 4.5e-05 |
| European (non-Finnish)37 / 1,163,708 | 3.2e-05 |
| Remaining individuals1 / 61,684 | 1.6e-05 |
| African/African American1 / 74,450 | 1.3e-05 |
0 alternate alleles recorded in 4 other groups: European (Finnish), Amish, South Asian, Ashkenazi Jewish.
gnomAD v2.1
AF 1.6e-05 · 4 / 250,820 alleles · 0 hom · FAF 2.9e-06
| Remaining individuals1 / 6,108 | 0.00016 |
| Admixed American1 / 34,578 | 2.9e-05 |
| European (non-Finnish)2 / 113,300 | 1.8e-05 |
0 alternate alleles recorded in 5 other groups: African/African American, Ashkenazi Jewish, East Asian, European (Finnish), South Asian.
gnomAD-Canada
AF 0.00011 · 2 / 18,416 alleles · 0 hom · FAF 0.00042
| amr2 / 838 | 0.0024 |
0 alternate alleles recorded in 8 other groups: afr, asj, eas, fin, mid, nfe, oth, sas.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 3.26226e-05; MAF= 0.00326%, 52/1593986 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000225225; MAF= 0.02252%, 1/4440 alleles, homozygotes = 0); grpmax FAF= 9.008e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59477e-05; MAF= 0.00159%, 4/250820 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00016372; MAF= 0.01637%, 1/6108 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000108601; MAF= 0.01086%, 2/18416 alleles, homozygotes = 0) and has highest observed frequency in the amr population (AF= 0.00238663; grpmax FAF95= 0.00042326).
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.516
- BayesDel
- 0.024
How the predictions were used
BP4 SupportingFor PMS2 missense variants, the VCEP prioritizes the HCI prior. This variant has an HCI prior probability of 0.0446, which is below the BP4 threshold of <0.11, supporting benign computational evidence. SpliceAI also predicts no splice impact with a max delta score of 0.00. Details ▾Hide ▴
Rule
For PMS2 missense variants, BP4_Supporting is met when the HCI prior probability is <0.11.
Evidence considered
- HCI prior probability 0.0446
- SpliceAI max delta score 0.00
- REVEL 0.516
- BayesDel 0.0236541
Sources
PP3 For PMS2 missense variants, the VCEP prioritizes the HCI prior. This variant has an HCI prior probability of 0.0446, which is below the PP3 thresholds of >0.68 for Supporting and >0.81 for Moderate, so PP3 is not met. SpliceAI also predicts no splice impact with a max delta score of 0.00. Details ▾Hide ▴
Rule
For PMS2 missense variants, PP3 requires HCI prior >0.68 (Supporting) or >0.81 (Moderate).
Evidence considered
- HCI prior probability 0.0446
- SpliceAI max delta score 0.00
- REVEL 0.516
- BayesDel 0.0236541
Sources
BP7 N/AThis variant is a missense substitution rather than a synonymous or qualifying intronic change, so BP7 does not apply. Details ▾Hide ▴
Evidence considered
- p.(Glu81Lys) is a missense variant
- PMS2 VCEP BP7 is for synonymous or qualifying intronic variants
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.516. BayesDel score = 0.0236541. HCI prior probability for pathogenicity = 0.0446. MAPP score = 3.49. Custom PP2 score = 0.774.
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.No paper-specific finding is recorded.
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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.No paper-specific finding is recorded.
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PMID 26467025 ↗A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.No paper-specific finding is recorded.
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PMID 26552419 ↗Combined Microsatellite Instability, MLH1 Methylation Analysis, and Immunohistochemistry for Lynch Syndrome Screening in Endometrial Cancers From GOG210: An NRG Oncology and Gynecologic Oncology Group Study.Goodfellow PJ et al. · 2015No paper-specific finding is recorded.
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PMID 31992580 ↗Characterisation of heterozygous PMS2 variants in French patients with Lynch syndrome.Wang Q et al. · 2020No paper-specific finding is recorded.
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PMID 37894291 ↗DNA Mismatch Repair Gene Variant Classification: Evaluating the Utility of Somatic Mutations and Mismatch Repair Deficient Colonic Crypts and Endometrial Glands.Walker R et al. · 2023No paper-specific finding is recorded.
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PMID 11598466 ↗Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal cancer--supporting documentation.No paper-specific finding is recorded.
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
52 / 1,593,986 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
13 Uncertain significance · 1 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/182817/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/7-6043612-C-T?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr7-6003981-C-T?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/7-6003981-C-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000535.7%3Ac.241G…
- OncoKB ↗www.oncokb.org/gene/PMS2/E81K
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=125058926
- 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= 3.26226e-05; MAF= 0.00326%, 52/1593986 alleles, homozygotes = 0) and has highest observed frequency in the Middle Eastern population (AF= 0.000225225; MAF= 0.02252%, 1/4440 alleles, homozygotes = 0); grpmax FAF= 9.008e-05.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 1.59477e-05; MAF= 0.00159%, 4/250820 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 0.00016372; MAF= 0.01637%, 1/6108 alleles, homozygotes = 0); grpmax FAF= 2.93e-06.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.000108601; MAF= 0.01086%, 2/18416 alleles, homozygotes = 0) and has highest observed frequency in the amr population (AF= 0.00238663; grpmax FAF95= 0.00042326).
ClinVar
This variant has been reported in ClinVar as Uncertain significance (13 clinical laboratories) and as Benign (1 clinical laboratory) and as Uncertain Significance (1 clinical laboratory). (ClinVarID = 182817)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.516. BayesDel score = 0.0236541. HCI prior probability for pathogenicity = 0.0446. MAPP score = 3.49. Custom PP2 score = 0.774.
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 previously been reported in somatic cancers (COSMIC; COSV56222918, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.