About MSH2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MSH2 c.1619G>C, p.(Ser540Thr)
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 MSH2 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
PM2Supporting
PM2 · supporting
This variant is extremely rare in population databases. In gnomAD v4.1, the allele frequency is 8.67e-06 (14/1,613,934 alleles, no homozygotes) with a grpmax filtering allele frequency of 5.42e-06, which is below the InSiGHT MSH2 VCEP PM2_Supporting threshold of <0.00002 (<1 in 50,000 alleles). Absent from gnomAD v2.1 and gnomAD-Canada.
Benign criteria applied · 1
BP4Supporting
BP4 · supporting
Multiple lines of computational evidence suggest no impact on the gene product. The HCI prior probability for pathogenicity is 0.0006, well below the InSiGHT MSH2 VCEP BP4_Supporting threshold of <0.11. SpliceAI predicts no splicing impact (max delta = 0.03, <=0.1). REVEL score is 0.276 (neutral range), and BayesDel score is -0.242779 (benign prediction).
Recorded classification: Not classified
Richards et.al., 2015 - Combining rules v2.0.0 criteria-combination framework: matched Rule31 (Benign.Supporting >=1 + Pathogenic.Supporting >=1) with applied criteria: PM2 supporting, BP4 supporting benign; 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
14 / 1,613,934 alleles
gnomAD v4.1: 14 / 1,613,934 alleles. Recorded AF 8.67446e-06. Recorded homozygote count 0.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.030 maximum delta
Recorded SpliceAI maximum delta score: 0.030. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
4 reported laboratory submissions
3 Uncertain significance · 1 Benign.
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. MSH2, a DNA mismatch repair protein, is frequently mutated in colorectal, small bowel, and endometrial cancers.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
1 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV105858650, 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 MSH2 VCEP v2.0.0, with the data and sources behind each one.
29 criteria with recorded statuses: 2 met · 3 not met · 9 not assessed · 15 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_000251.3:c.1619G>C (p.Ser540Thr) is a missense variant in MSH2 exon 10. It is extremely rare in population databases (gnomAD v4.1 AF = 8.67e-06, 14/1,613,934 alleles), meeting PM2_Supporting under the InSiGHT MSH2 VCEP v2.0.0 threshold of <0.00002.
Multiple lines of computational evidence (HCI prior = 0.0006, SpliceAI max delta = 0.03, REVEL = 0.276, BayesDel = -0.242779) predict a neutral effect, meeting BP4_Supporting under the InSiGHT MSH2 VCEP v2.0.0 threshold of HCI prior < 0.11.
Functional data from a calibrated massively parallel assay (PMID:33357406) exists for MSH2 missense variants but the variant-specific LoF score for p.Ser540T could not be verified from the available full text; PS3/BS3 remain not assessed pending supplementary data review.
ClinVar reports this variant as Uncertain Significance (3 clinical laboratories) and Benign (1 clinical laboratory), with no expert panel review. PP5 is not applicable under this VCEP.
This variant has been observed in COSMIC (n=1 somatic occurrence) but does not lie in a statistically significant mutational hotspot.
No criteria match.
Met · 2
PM2 SupportingThis variant is extremely rare in population databases. In gnomAD v4.1, the allele frequency is 8.67e-06 (14/1,613,934 alleles, no homozygotes) with a grpmax filtering allele frequency of 5.42e-06, which is below the InSiGHT MSH2 VCEP PM2_Supporting threshold of <0.00002 (<1 in 50,000 alleles). Absent from gnomAD v2.1 and gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: AF = 8.67e-06 (14/1
- 613
- 934)
- grpmax FAF = 5.42e-06
- gnomAD v2.1: absent
- gnomAD-Canada: absent. All allele frequencies are below the VCEP PM2_Supporting threshold of 1/50
- 000 (0.00002).
Sources
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. The HCI prior probability for pathogenicity is 0.0006, well below the InSiGHT MSH2 VCEP BP4_Supporting threshold of <0.11. SpliceAI predicts no splicing impact (max delta = 0.03, <=0.1). REVEL score is 0.276 (neutral range), and BayesDel score is -0.242779 (benign prediction). Details ▾Hide ▴
Evidence considered
- HCI prior: 0.0006 (<0.11 BP4_Supporting threshold)
- SpliceAI max delta: 0.03 (<=0.1)
- REVEL: 0.276
- BayesDel: -0.242779. Computational evidence consistently predicts a neutral/benign effect.
Sources
Not met · 3 · evaluated, threshold not reached
PP3 Multiple lines of computational evidence do not support a deleterious effect. The HCI prior probability for pathogenicity is 0.0006, well below the PP3_Supporting threshold of >0.68. SpliceAI delta score is 0.03, well below the 0.2 threshold for predicted splice defects. REVEL score is 0.276, and BayesDel score is -0.242779, both in the neutral/benign range. Details ▾Hide ▴
Evidence considered
- HCI prior: 0.0006 (<0.68 PP3_Supporting threshold)
- SpliceAI max delta: 0.03 (<0.2)
- REVEL: 0.276
- BayesDel: -0.242779. No computational tool reaches the VCEP PP3 threshold.
Sources
BA1 The gnomAD v4.1 grpmax filtering allele frequency is 5.42e-06, far below the InSiGHT MSH2 VCEP BA1 threshold of >=0.001 (0.1%). The variant is rare in population databases and does not meet the stand-alone benign allele frequency threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 5.42e-06
- BA1 threshold = >=0.001. Not met.
Sources
BS1 The gnomAD v4.1 grpmax filtering allele frequency is 5.42e-06, below the InSiGHT MSH2 VCEP BS1 threshold of >=0.0001 (0.01%). The variant is too rare in population databases to meet BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 5.42e-06
- BS1 threshold = >=0.0001. Not met.
Sources
Not assessed · 9 · no assessment recorded
PS1 No evidence found of a different nucleotide change encoding the same amino acid substitution (p.Ser540Thr) previously classified as Pathogenic or Likely Pathogenic by the InSiGHT MSH2 VCEP. Details ▾Hide ▴
Still missing
- No reported alternative nucleotide change at codon 540 producing p.Ser540Thr with prior VCEP classification.
PS2 No de novo data available for this variant. No publications or clinical records report a de novo occurrence of NM_000251.3:c.1619G>C with confirmed maternity and paternity. Details ▾Hide ▴
Still missing
- No de novo reports identified in literature or clinical databases.
PS3 PMID 33357406 (Jia et al. 2021) is a calibrated functional assay for MSH2 missense variants listed in the VCEP Functional-assay-SVI-documentation-MMR.xlsx. The paper reports a massively parallel screen covering 94.4% of possible MSH2 missense variants, but the full text does not name p.Ser540T specifically and the variant-specific LoF score could not be verified from the available text. The supplementary data tables are required to extract the S540T LoF score and determine whether it meets the calibrated functional odds threshold for PS3 (OddsPath > 2.08 for supporting, > 4.3 for moderate, > 18.7 for strong). Details ▾Hide ▴
Evidence considered
- Massively parallel functional screen of MSH2 missense variants (PMID:33357406) is a VCEP-recognized calibrated assay
- but the p.Ser540T LoF score could not be confirmed from the available full text.
Still missing
- Requires extraction of the p.Ser540T LoF score from PMID:33357406 supplementary data to determine whether the variant meets PS3 or BS3 calibrated functional assay thresholds.
Sources
PP1 No co-segregation data available for this variant. No pedigrees with combined Bayes Likelihood Ratio calculations were identified. Details ▾Hide ▴
Still missing
- No co-segregation or pedigree data available.
PP4 No tumor MSI or IHC data available for this variant. The InSiGHT MSH2 VCEP PP4 criterion requires specific numbers of CRC/Endometrial MSI-H tumors with MMR protein expression status consistent with the variant location. No such data were identified in the evidence brief or literature. Details ▾Hide ▴
Still missing
- No tumor MSI or IHC data from variant carriers available for PP4 assessment.
BS2 No evidence of co-occurrence in trans with a known pathogenic MSH2 variant in a patient with colorectal cancer after age 45 without CMMRD features. Confirmation of phase would require parental testing. Details ▾Hide ▴
Still missing
- No data on in trans co-occurrence with pathogenic MSH2 variants.
BS3 PMID 33357406 (Jia et al. 2021) is a calibrated functional assay for MSH2 missense variants recognized by the VCEP. The paper reports that 89.4% of MSH2 missense variants are functionally neutral. However, the variant-specific LoF score for p.Ser540T could not be verified from the available full text. The supplementary data tables are required to confirm whether the S540T LoF score meets the VCEP BS3_Strong (functional odds <=0.05) or BS3_Supporting (>0.05 & <=0.48) thresholds. Details ▾Hide ▴
Evidence considered
- Massively parallel functional screen of MSH2 missense variants (PMID:33357406) is a VCEP-recognized calibrated assay
- but the p.Ser540T LoF score could not be confirmed from the available full text.
Still missing
- Requires extraction of the p.Ser540T LoF score from PMID:33357406 supplementary data to determine whether the variant meets PS3 or BS3 calibrated functional assay thresholds.
Sources
BS4 No lack-of-segregation data available for this variant. No pedigrees with combined Bayes Likelihood Ratio calculations were identified to support BS4. Details ▾Hide ▴
Still missing
- No segregation or lack-of-segregation data available.
BP5 No tumor data available demonstrating MSS status or loss of MMR protein expression inconsistent with MSH2 involvement. The VCEP BP5 criterion requires documented tumors with MSS and/or inconsistent IHC findings. Details ▾Hide ▴
Still missing
- No tumor MSS/IHC data available.
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/AMissense substitution; not a null variant (nonsense, frameshift, or canonical splice site). PVS1 is restricted to null variants under the InSiGHT MSH2 VCEP v2.0.0 decision tree. Details ▾Hide ▴
Evidence considered
- Missense variant c.1619G>C (p.Ser540Thr) does not introduce a premature termination codon or disrupt canonical splice sites
- classified as 'other' bucket per ClinGen SVI PVS1 framework.
Sources
pvs1_variant_assessmentpvs1_gene_context
PS4 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'Due to the availability of tumor IHC data for variant classification (see PP4), PS4 has not been utilized for MMR variant classification using proband counting.' Details ▾Hide ▴
PM1 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'There are no recognized mutational hot spots that could be used for classification purposes. While there are functional domains in the MMR genes, the distribution of pathogenic variants is generalized over all the domains.' Details ▾Hide ▴
PM3 N/AMSH2/Lynch syndrome is autosomal dominant; PM3 (detected in trans with pathogenic variant for recessive disorders) is not applicable in the germline heterozygous context. While the InSiGHT VCEP does define PM3 for CMMRD biallelic assessment, no CMMRD context is indicated for this case. Details ▾Hide ▴
Evidence considered
- Autosomal dominant disorder
- PM3 not applicable in heterozygous Lynch syndrome context.
PM4 VCEPMissense substitution; PM4 applies to protein length changes from in-frame deletions/insertions or stop-loss variants. The VCEP further specifies that protein length change from in-frame variants is not used due to lack of evidence. Details ▾Hide ▴
PM5 N/ANo different missense change at codon 540 previously classified as Pathogenic or Likely Pathogenic by the InSiGHT MSH2 VCEP. pm5_candidates.json found no comparator variants at this residue. Details ▾Hide ▴
Evidence considered
- No same-residue missense comparator variants with VCEP P/LP classification found.
Sources
pm5_candidates
PM6 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. PM6 is set to 'Not applicable' for all strength levels in the VCEP criteria; PS2 point system is used instead for de novo assessment. Details ▾Hide ▴
Evidence considered
- VCEP explicitly excludes PM6 from use
- PS2 point system is the designated de novo criterion.
Sources
PP2 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'Missense variant in a gene with low rate of benign missense changes does not apply.' Details ▾Hide ▴
PP5 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
BP1 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'Missense variant in a gene where only loss of function causes disease is not applicable.' Details ▾Hide ▴
Evidence considered
- VCEP explicitly excludes BP1 from use for missense variants in MSH2.
Sources
BP2 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'BS2 is used instead.' Details ▾Hide ▴
BP3 VCEPMissense substitution; BP3 applies only to in-frame deletions/insertions in a repetitive region without known function. Details ▾Hide ▴
BP6 VCEPNot applicable under InSiGHT MSH2 VCEP v2.0.0. The VCEP states: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond -21/+7. NM_000251.3:c.1619G>C is a missense substitution (p.Ser540Thr), not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP7 restricted to synonymous and intronic variants per VCEP.
Sources
PS5 N/APS5 is not included as a criterion in the InSiGHT MSH2 VCEP v2.0.0 criteria set and is not available for use in this framework. Details ▾Hide ▴
Identifiers
- Gene
- MSH2
- Transcript
- NM_000251.3
- Coding (HGVS c.)
- NM_000251.3:c.1619G>C
- Protein (HGVS p.)
- NP_000242.1:p.(Ser540Thr)
- GRCh38
- chr2:47466766 G>C
- GRCh37
- chr2:47693905 G>C
- ClinVar
- 487021
- COSMIC
- COSV105858650
Gene diagram
Every interpreted variant in MSH2, mapped onto the exon structure of NM_000251.3. Select a row to find it on the plot.
MSH2NM_000251.3
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 MSH2
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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
14 / 1,613,934 alleles
AF 8.67e-06 · 0 homozygotes · FAF 5.42e-06
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 8.7e-06 · 14 / 1,613,934 alleles · 0 hom · FAF 5.4e-06
| Remaining individuals2 / 62,494 | 3.2e-05 |
| European (non-Finnish)12 / 1,179,880 | 1e-05 |
0 alternate alleles recorded in 8 other groups: Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 8.67446e-06; MAF= 0.00087%, 14/1613934 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.20031e-05; MAF= 0.00320%, 2/62494 alleles, homozygotes = 0); grpmax FAF= 5.42e-06.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.276
- BayesDel
- -0.243
How the predictions were used
BP4 SupportingMultiple lines of computational evidence suggest no impact on the gene product. The HCI prior probability for pathogenicity is 0.0006, well below the InSiGHT MSH2 VCEP BP4_Supporting threshold of <0.11. SpliceAI predicts no splicing impact (max delta = 0.03, <=0.1). REVEL score is 0.276 (neutral range), and BayesDel score is -0.242779 (benign prediction). Details ▾Hide ▴
Evidence considered
- HCI prior: 0.0006 (<0.11 BP4_Supporting threshold)
- SpliceAI max delta: 0.03 (<=0.1)
- REVEL: 0.276
- BayesDel: -0.242779. Computational evidence consistently predicts a neutral/benign effect.
Sources
PP3 Multiple lines of computational evidence do not support a deleterious effect. The HCI prior probability for pathogenicity is 0.0006, well below the PP3_Supporting threshold of >0.68. SpliceAI delta score is 0.03, well below the 0.2 threshold for predicted splice defects. REVEL score is 0.276, and BayesDel score is -0.242779, both in the neutral/benign range. Details ▾Hide ▴
Evidence considered
- HCI prior: 0.0006 (<0.68 PP3_Supporting threshold)
- SpliceAI max delta: 0.03 (<0.2)
- REVEL: 0.276
- BayesDel: -0.242779. No computational tool reaches the VCEP PP3 threshold.
Sources
BP7 N/ABP7 applies only to synonymous (silent) or intronic variants at or beyond -21/+7. NM_000251.3:c.1619G>C is a missense substitution (p.Ser540Thr), not a synonymous or intronic variant. Details ▾Hide ▴
Evidence considered
- Missense substitution
- BP7 restricted to synonymous and intronic variants per VCEP.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.276. BayesDel score = -0.242779. HCI prior probability for pathogenicity = 0.0006. MAPP score = 2.19. Custom PP2 score = 0.003.
7 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
-
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.
-
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 interpretation of sequence variants. Provides the generic framework for variant classification but does not discuss any specific variants.Does not name this variant
-
PMID 33357406 ↗Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.Jia X et al. · 2021Massively parallel functional screen of 17,746 possible MSH2 missense variants in human HAP1 cells using 6-thioguanine selection. The paper reports that 89.4% of missense variants are functionally neutral and the functional effect map covers 94.4% of possible substitutions. The p.Ser540Thr variant was not specifically named in the full text; its LoF score resides in supplementary data tables not included in the available text.Does not name this variant
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PMID 20301390 ↗Lynch Syndrome.Adam MP et al. · 1993No paper-specific finding is recorded.
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PMID 22167527 ↗Identification of individuals at risk for Lynch syndrome using targeted evaluations and genetic testing: National Society of Genetic Counselors and the Collaborative Group of the Americas on Inherited Colorectal Cancer joint practice guideline.Weissman SM et al. · 2012No paper-specific finding is recorded.
-
PMID 23408351 ↗Revised guidelines for the clinical management of Lynch syndrome (HNPCC): recommendations by a group of European experts.Revised European guidelines for clinical management of Lynch syndrome. Discusses surveillance and management recommendations for MMR gene mutation carriers at the gene level.Does not name this variant
-
PMID 23788249 ↗ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing.Green RC et al. · 2013ACMG recommendations for reporting incidental findings in clinical exome and genome sequencing. Lists MSH2 among genes recommended for return of incidental findings.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
14 / 1,613,934 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.030
Open source ↗
ClinVar
3 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 ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1577628936
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/487021/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-47693905-G-C?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-47466766-G-C?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-47466766-G-C
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000251.3%3Ac.1619…
- OncoKB ↗www.oncokb.org/gene/MSH2/S540T
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=124537520
- 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= 8.67446e-06; MAF= 0.00087%, 14/1613934 alleles, homozygotes = 0) and has highest observed frequency in the Remaining individuals population (AF= 3.20031e-05; MAF= 0.00320%, 2/62494 alleles, homozygotes = 0); grpmax FAF= 5.42e-06.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (3 clinical laboratories) and as Benign (1 clinical laboratory). (ClinVarID = 487021)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.03). REVEL score = 0.276. BayesDel score = -0.242779. HCI prior probability for pathogenicity = 0.0006. MAPP score = 2.19. Custom PP2 score = 0.003.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. MSH2, a DNA mismatch repair protein, is frequently mutated in colorectal, small bowel, and endometrial cancers.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV105858650, n = 1 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.