About MSH2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MSH2 c.1316_1318del, p.(Pro439del)
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 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: 0
Pathogenic criteria applied · 1
PM2Supporting
PM2 · supporting
NM_000251.3:c.1316_1318del is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. This meets the InSiGHT MSH2 VCEP v2.0.0 PM2_Supporting threshold of absent/extremely rare allele frequency <0.00002 (<1 in 50,000 alleles) in gnomAD v4.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
Richards et.al., 2015 - Combining rules v2.0.0 criteria-combination framework was evaluated deterministically with applied criteria: PM2 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
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.010 maximum delta
Recorded SpliceAI maximum delta score: 0.010. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
7 reported laboratory submissions
4 Uncertain significance · 2 Likely pathogenic · 1 likely pathogenic. 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. 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
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 MSH2 VCEP v2.0.0, with the data and sources behind each one.
29 criteria with recorded statuses: 1 met · 3 not met · 9 not assessed · 16 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.1316_1318del is an in-frame deletion of 3 nucleotides in exon 8 of MSH2, resulting in p.Pro439del. This variant is absent from all population databases including gnomAD v2.1, v4.1, and gnomAD-Canada, meeting the InSiGHT MSH2 VCEP v2.0.0 PM2_Supporting criterion.
The InSiGHT MSH2 VCEP v2.0.0 declares multiple criteria as not applicable for MMR gene classification: PM1 (no recognized mutational hotspots), PM4 (protein length change from in-frame variants not used), PS4 (IHC data preferred over proband counting), PP5, BP6, BP1, BP2, BP3, PM6, and PP2.
PVS1 is not applicable to this in-frame deletion under VCEP rules as it does not introduce a premature termination codon, does not involve canonical splice sites, and no patient mRNA assay data is available. PS1 and PM5 are not applicable as they are defined for missense substitutions only.
PP3 and BP4 are not applicable to this in-frame deletion under VCEP rules, which specify HCI prior thresholds for missense variants and SpliceAI thresholds for intronic/synonymous variants. SpliceAI predicts no splicing impact (max delta = 0.01), consistent with the variant's location within exon 8 and its in-frame nature.
No functional assay data (PS3/BS3), segregation data (PP1/BS4), tumor phenotype data (PP4/BP5), de novo reports (PS2), or trans co-occurrence data (BS2) are available for this variant. The ClinVar entry (Variation ID 90623) reports classifications of Uncertain significance by 4 clinical laboratories and Likely pathogenic by 2 laboratories, with review status 'criteria provided, single submitter' at the star-level aggregate.
Eight publications were reviewed for this variant, including full-text analysis where available. None of the reviewed publications mention NM_000251.3:c.1316_1318del specifically. The publications include methodological papers (SIFT Indel), ACMG/AMP guideline documents, Lynch syndrome management guidelines, and hereditary cancer syndrome reviews.
Based on the InSiGHT MSH2 VCEP v2.0.0 framework, the only applicable criterion met is PM2_Supporting (absent from gnomAD). With a single supporting pathogenic criterion and no benign criteria, the evidence is insufficient for classification beyond Variant of Uncertain Significance per the VCEP combination rules. Additional evidence from tumor studies, segregation analysis, or functional assays would be required to reach a more definitive classification.
No criteria match.
Met · 1
PM2 SupportingNM_000251.3:c.1316_1318del is absent from gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0. This meets the InSiGHT MSH2 VCEP v2.0.0 PM2_Supporting threshold of absent/extremely rare allele frequency <0.00002 (<1 in 50,000 alleles) in gnomAD v4. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (0 alleles)
- Absent from gnomAD v4.1 (0 alleles)
- Absent from gnomAD-Canada v1.0 (0 alleles)
- VCEP PM2_Supporting threshold: AF <0.00002 in gnomAD v4
Sources
Not met · 3 · evaluated, threshold not reached
PVS1 NM_000251.3:c.1316_1318del is an in-frame deletion (p.Pro439del) in exon 8 of MSH2. The InSiGHT MSH2 VCEP v2.0.0 PVS1 criteria are restricted to nonsense/frameshift variants introducing a premature termination codon, large genomic alterations, canonical splice site variants, or mRNA-confirmed splicing aberrations. This in-frame deletion does not introduce a PTC, does not affect a canonical splice site, and no patient mRNA assay data is available. PVS1 is not applicable to this variant type under the VCEP framework. Details ▾Hide ▴
Evidence considered
- In-frame deletion of 3 nucleotides (c.1316_1318del) in exon 8
- preserving the reading frame
- VCEP PVS1 rules cover PTC-introducing variants
- large CNVs
- canonical splice
- and mRNA-confirmed splicing
- none apply to in-frame deletions without mRNA data
Still missing
- No patient mRNA assay data available to assess potential splicing aberration or allelic expression
Sources
BA1 BA1 requires gnomAD v4 Grpmax filtering allele frequency >=0.001 (0.1%). NM_000251.3:c.1316_1318del is absent from gnomAD v4.1, well below the BA1 threshold. BA1 is not met. Details ▾Hide ▴
BS1 BS1 requires gnomAD v4 Grpmax filtering allele frequency >=0.0001 and <0.001 (0.01-0.1%). NM_000251.3:c.1316_1318del is absent from gnomAD v4.1, below the BS1 threshold. BS1 is not met. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v4.1
- VCEP BS1 threshold: AF >=0.0001 and <0.001
Sources
Not assessed · 9 · no assessment recorded
PS2 No de novo occurrence data is available for NM_000251.3:c.1316_1318del. Without confirmed de novo observations with maternity and paternity confirmation, PS2 cannot be assessed. Details ▾Hide ▴
Still missing
- No de novo reports identified for this variant
PS3 No variant-specific functional assay data is available for NM_000251.3:c.1316_1318del. The InSiGHT VCEP functional assay documentation (Functional-assay-SVI-documentation-MMR.xlsx) lists calibrated assays validated for MMR gene missense, splice site, and synonymous variants, but no assay results are reported for this in-frame deletion. OncoKB lists this variant as 'Unknown Oncogenic Effect' with no curated functional evidence. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet lists calibrated assays but no variant-specific data for c.1316_1318del
- OncoKB classification: Unknown Oncogenic Effect
Still missing
- No functional assay results for this in-frame deletion in any calibrated MMR assay system
Sources
oncokb ↗vcep_functional_assay_svi_documentation_mmr
PP1 No co-segregation data is available for NM_000251.3:c.1316_1318del. Segregation analysis with Bayes Likelihood Ratio calculation would be required to apply PP1 at any strength level under the VCEP framework. Details ▾Hide ▴
Still missing
- No family segregation data available
PP4 No tumor MSI/IHC data is available for patients carrying NM_000251.3:c.1316_1318del. PP4 under the InSiGHT VCEP requires CRC/endometrial MSI-H tumors and/or loss of MMR protein expression consistent with the variant location. Without tumor phenotype data, PP4 cannot be assessed. Details ▾Hide ▴
Still missing
- No tumor MSI or IHC data available for variant carriers
BS2 No data is available on co-occurrence of NM_000251.3:c.1316_1318del in trans with a known pathogenic MSH2 variant. BS2 requires phase-confirmed co-occurrence in a patient with colorectal cancer after age 45 (or other LS cancer above median onset age) without CMMRD features. Details ▾Hide ▴
Still missing
- No trans co-occurrence data available
BS3 No variant-specific functional assay data demonstrating normal protein function is available for NM_000251.3:c.1316_1318del. No calibrated functional assay results with functional odds for pathogenicity <=0.48 (BS3_Supporting) or <=0.05 (BS3) have been reported for this variant. Details ▾Hide ▴
Evidence considered
- VCEP functional assay spreadsheet does not list assay results for c.1316_1318del
Still missing
- No functional assay data for this variant in any calibrated MMR system
Sources
vcep_functional_assay_svi_documentation_mmr
BS4 No segregation data is available to evaluate lack of co-segregation with disease. BS4 requires pedigree data with combined Bayes Likelihood Ratio calculation showing lack of co-segregation. Details ▾Hide ▴
Still missing
- No family segregation/lack of segregation data available
BP5 No data is available on the presence of an alternate molecular basis for disease in patients carrying NM_000251.3:c.1316_1318del. BP5 requires evidence of an alternate cause (e.g., BRAF V600E, MLH1 methylation, or another pathogenic variant explaining the phenotype). Details ▾Hide ▴
Still missing
- No data on alternate molecular diagnoses or somatic findings in variant carriers
PS5 PS5 is not defined in the InSiGHT MSH2 VCEP v2.0.0 criteria set. No evidence is available to support a generic PS5 assessment for this variant. Details ▾Hide ▴
Still missing
- PS5 not defined by VCEP
- no evidence collected for this criterion
Not applicable · 16· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies to missense substitutions encoding the same amino acid change as an established pathogenic variant, or variants affecting the same non-canonical splice nucleotide. NM_000251.3:c.1316_1318del is an in-frame deletion, not a missense substitution or splice variant. Not applicable to this variant type. Details ▾Hide ▴
Evidence considered
- VCEP PS1 is defined for missense substitutions and non-canonical splice variants only
Sources
PS4 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares PS4 as not applicable. Per the VCEP: '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 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares PM1 as not applicable. Per the VCEP: '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/APM3 was designated for skip by the adjudication workflow. Not assessed in this evaluation. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares PM4 as not applicable. Per the VCEP: 'Protein length change from an in-frame variant is not used due to lack of evidence.' Details ▾Hide ▴
Evidence considered
- VCEP declares PM4 'Not applicable' for MSH2
- in-frame deletions/insertions not used for classification
Sources
PM5 N/APM5 applies to missense changes at an amino acid residue where a different missense change has been classified as pathogenic. NM_000251.3:c.1316_1318del is an in-frame deletion (p.Pro439del), not a missense substitution. The PM5 candidate analysis confirmed that this variant class is not eligible for classic same-residue missense PM5. Details ▾Hide ▴
Evidence considered
- VCEP PM5 is defined for missense substitutions only
- PM5 candidate pipeline confirms variant is not missense-like
Sources
cspec ↗pm5_candidates
PM6 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares PM6 as not applicable. Per the VCEP: PM6 is designated 'Not applicable' for this gene. Details ▾Hide ▴
PP2 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares PP2 as not applicable. Per the VCEP: 'Missense variant in a gene with low rate of benign missense changes does not apply.' Details ▾Hide ▴
PP3 N/AThe InSiGHT MSH2 VCEP v2.0.0 PP3 rules apply to missense variants (HCI prior probability thresholds) or predicted splice defects at non-canonical splice nucleotides (SpliceAI delta score >=0.2). NM_000251.3:c.1316_1318del is an in-frame deletion, not a missense variant, and SpliceAI predicts no splicing impact (max delta = 0.01). The variant does not fall within any VCEP-defined PP3 evidence category. Details ▾Hide ▴
Evidence considered
- HCI prior not available (in-frame deletion
- not missense)
- SpliceAI max delta score = 0.01 (no predicted splice impact)
- VCEP PP3 rules cover missense HCI priors and non-canonical splice predictions only
Sources
PP5 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares PP5 as 'Not Applicable for this VCEP'. Per the VCEP: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
BP1 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares BP1 as not applicable. Per the VCEP: 'Missense variant in a gene where only loss of function causes disease is not applicable.' Details ▾Hide ▴
BP2 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares BP2 as not applicable. Per the VCEP: 'BS2 is used instead.' Details ▾Hide ▴
Evidence considered
- VCEP declares BP2 'Not applicable'
- BS2 replaces BP2 in MMR gene classification
Sources
BP3 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares BP3 as not applicable. Per the VCEP: 'In-frame deletions/insertions in a repetitive region without a known function is not used.' Details ▾Hide ▴
BP4 N/AThe InSiGHT MSH2 VCEP v2.0.0 BP4 rules apply to missense variants (HCI prior probability <0.11) or intronic/synonymous variants (SpliceAI delta score <=0.1). NM_000251.3:c.1316_1318del is an in-frame deletion, not a missense, intronic, or synonymous variant. The variant does not fall within any VCEP-defined BP4 evidence category. Details ▾Hide ▴
Evidence considered
- HCI prior not available (in-frame deletion
- not missense)
- SpliceAI max delta = 0.01
- but BP4 SpliceAI rule applies to intronic/synonymous variants only
- VCEP BP4 rules cover missense HCI priors and intronic/synonymous SpliceAI only
Sources
BP6 VCEPThe InSiGHT MSH2 VCEP v2.0.0 declares BP6 as 'Not Applicable for this VCEP'. Per the VCEP: 'This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.' Details ▾Hide ▴
BP7 N/ABP7 applies to synonymous (silent) or intronic variants at or beyond -21/+7. NM_000251.3:c.1316_1318del is an in-frame deletion within exon 8, resulting in the deletion of proline at codon 439. This is neither a synonymous nor an intronic variant. BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- VCEP BP7 is defined for synonymous and intronic variants only
- c.1316_1318del is an exonic in-frame deletion
- not synonymous
Sources
Identifiers
- Gene
- MSH2
- Transcript
- NM_000251.3
- Coding (HGVS c.)
- NM_000251.3:c.1316_1318del
- Protein (HGVS p.)
- NP_000242.1:p.(Pro439del)
- GRCh38
- chr2:47445583 ACTC>A
- GRCh37
- chr2:47672722 ACTC>A
- ClinVar
- 90623
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
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 N/AThe InSiGHT MSH2 VCEP v2.0.0 PP3 rules apply to missense variants (HCI prior probability thresholds) or predicted splice defects at non-canonical splice nucleotides (SpliceAI delta score >=0.2). NM_000251.3:c.1316_1318del is an in-frame deletion, not a missense variant, and SpliceAI predicts no splicing impact (max delta = 0.01). The variant does not fall within any VCEP-defined PP3 evidence category. Details ▾Hide ▴
Evidence considered
- HCI prior not available (in-frame deletion
- not missense)
- SpliceAI max delta score = 0.01 (no predicted splice impact)
- VCEP PP3 rules cover missense HCI priors and non-canonical splice predictions only
Sources
BP4 N/AThe InSiGHT MSH2 VCEP v2.0.0 BP4 rules apply to missense variants (HCI prior probability <0.11) or intronic/synonymous variants (SpliceAI delta score <=0.1). NM_000251.3:c.1316_1318del is an in-frame deletion, not a missense, intronic, or synonymous variant. The variant does not fall within any VCEP-defined BP4 evidence category. Details ▾Hide ▴
Evidence considered
- HCI prior not available (in-frame deletion
- not missense)
- SpliceAI max delta = 0.01
- but BP4 SpliceAI rule applies to intronic/synonymous variants only
- VCEP BP4 rules cover missense HCI priors and intronic/synonymous SpliceAI only
Sources
BP7 N/ABP7 applies to synonymous (silent) or intronic variants at or beyond -21/+7. NM_000251.3:c.1316_1318del is an in-frame deletion within exon 8, resulting in the deletion of proline at codon 439. This is neither a synonymous nor an intronic variant. BP7 is not applicable. Details ▾Hide ▴
Evidence considered
- VCEP BP7 is defined for synonymous and intronic variants only
- c.1316_1318del is an exonic in-frame deletion
- not synonymous
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
8 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 12907901 ↗Microsatellite instability and mutations in DNA mismatch repair genes in sporadic colorectal cancers.Jeong SY et al. · 2003Investigates microsatellite instability and MMR gene mutations (hMLH1, hMSH2) in 230 sporadic colorectal cancers using BAT-26 marker and immunohistochemistry. NM_000251.3:c.1316_1318del was not identified in this paper.Does not name this variant
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PMID 24194902 ↗SIFT Indel: predictions for the functional effects of amino acid insertions/deletions in proteins.Hu J et al. · 2013Describes the SIFT Indel algorithm for predicting functional effects of amino acid insertions/deletions. NM_000251.3:c.1316_1318del was not specifically analyzed or mentioned in this paper.Does not name this variant
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PMID 25645574 ↗ACG clinical guideline: Genetic testing and management of hereditary gastrointestinal cancer syndromes.ACG clinical guideline for genetic testing and management of hereditary gastrointestinal cancer syndromes including Lynch syndrome. NM_000251.3:c.1316_1318del was not mentioned in this guideline document.Does not name this variant
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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.ACMG/AMP standards and guidelines for interpretation of sequence variants. This foundational document defines the generic ACMG/AMP criteria framework but does not discuss NM_000251.3:c.1316_1318del specifically.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 pathogenicity assessments in Mendelian disorders. NM_000251.3:c.1316_1318del was not specifically analyzed in this paper.Does not name this variant
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PMID 11598466 ↗Practice parameters for the identification and testing of patients at risk for dominantly inherited colorectal cancer--supporting documentation.Practice parameters for identification and testing of patients at risk for dominantly inherited colorectal cancer. NM_000251.3:c.1316_1318del was not identified in this document.Does not name this variant
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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 (Mallorca group recommendations). NM_000251.3:c.1316_1318del was not mentioned in this guideline document.Does not name this variant
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PMID 23535968 ↗Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists.Guideline for clinical geneticists on informing family members of individuals with Lynch syndrome about predictive DNA testing. NM_000251.3:c.1316_1318del was not mentioned in this guideline document.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.010
Open source ↗
ClinVar
4 Uncertain significance · 2 Likely pathogenic · 1 likely pathogenic
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/?term=NM_000251.3%3Ac.1316_1318del
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-47672722-ACTC-A?dataset=gno…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-47445583-ACTC-A?dataset=…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-47445583-ACTC-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000251.3%3Ac.1316…
- OncoKB ↗www.oncokb.org/gene/MSH2/P439del
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MSH2+c.1316_1318del
- 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
Absent from gnomAD v4.1.
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 (4 clinical laboratories) and as Likely pathogenic (2 clinical laboratories) and as likely pathogenic (1 clinical laboratory). (ClinVarID = 90623)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).
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 not previously been reported in somatic cancers (COSMIC).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.