About MSH2
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MSH2 c.367-1G>A, p.?
Classification
Pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is pathogenic. Select a step to read what it means.
Pathogenic.A pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen MSH2 VCEP v2.0. 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: 3
Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Very strong
PVS1 · very strong
Canonical splice acceptor variant (IVS2-1G>A, NM_000251.2:c.367-1G>A) disrupting the invariant AG dinucleotide. cDNA analysis from patient blood (Wolf et al., PMID:15926618) confirmed the variant generates a new splice acceptor site 1 bp downstream, resulting in deletion of a guanine (r.367delg) and a frameshift predicted to produce a premature termination codon (p.122fsX173) subject to nonsense-mediated decay. Under InSiGHT MMR VCEP v2.0 PVS1 rules, IVS+/-1 or IVS+/-2 variants where exon skipping or cryptic splice site use disrupts the reading frame and is predicted to undergo NMD qualify for PVS1 at very_strong strength. Confirmed by patient-derived mRNA assay; no additional independent confirmation required as this is a canonical splice site variant.
PM2Supporting
PM2 · supporting
Absent from gnomAD v2.1 (exomes), gnomAD v4.1, and gnomAD-Canada v1.0. Under InSiGHT MMR VCEP v2.0, PM2_Supporting applies when allele frequency is <0.00002 (<1 in 50,000 alleles) in gnomAD v4. The variant is completely absent from all population databases, satisfying this threshold.
PP5Supporting
PP5 · supporting
Expert panel International Society for Gastrointestinal Hereditary Tumours (InSiGHT) classified as Likely pathogenic.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Pathogenic
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH2 Version 2.0 v2.0 criteria-combination framework: matched Rule4 (1 Pathogenic.Very Strong + Pathogenic.Supporting >=2) with applied criteria: PVS1 very strong, PM2 supporting, PP5 supporting; maps to Pathogenic.
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
0.990 maximum delta
Recorded SpliceAI maximum delta score: 0.990. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions
2 Likely pathogenic · 1 Pathogenic. ClinVar API review status: reviewed by expert panel.
No screenshot for this evidence
Functional evidence
Not recorded
No standalone functional evidence summary is recorded in evidence_summary.functional.
No listed criterion applied
OncoKB ↗
Somatic evidence
No matching record reported
This variant has not previously been reported in somatic cancers (COSMIC).
Context only
COSMIC ↗
For specialists
Technical detail
ACMG/AMP criteria under ClinGen MSH2 VCEP v2.0, with the data and sources behind each one.
27 criteria with recorded statuses: 3 met · 12 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_000251.2:c.367-1G>A is a canonical splice acceptor variant (IVS2-1G>A) disrupting the invariant AG dinucleotide of intron 2 in MSH2, a gene for which loss of function is an established mechanism for Lynch syndrome.
SpliceAI predicts strong splice disruption with a maximum delta score of 0.99 (acceptor loss 0.99), and cDNA analysis from patient lymphocytes (Wolf et al. 2005, PMID:15926618) confirmed aberrant splicing: the variant creates a new splice acceptor 1 bp downstream, resulting in deletion of a guanine (r.367delg) and a frameshift (p.122fsX173) predicted to introduce a premature termination codon subject to nonsense-mediated decay.
Under InSiGHT MMR VCEP v2.0, canonical splice site variants at IVS+/-1 or IVS+/-2 where exon skipping or cryptic splice site use disrupts the reading frame and is predicted to undergo NMD qualify for PVS1 at very_strong strength. The premature termination codon at position 173 is well upstream of the MSH2 NMD boundary at codon 891.
The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada, meeting the VCEP PM2_Supporting threshold of <0.00002 allele frequency. It was also absent from 100 healthy control alleles in the Wolf et al. study.
ClinVar classifies this variant as Likely pathogenic (Variation ID 91075), reviewed by the InSiGHT expert panel, consistent with the VCEP assessment.
No benign or conflicting evidence was identified. BS3 is contradicted by the confirmed splicing aberration. BP4 is contradicted by the strong SpliceAI prediction. PP3 is not applied per VCEP rules prohibiting combination with PVS1 for canonical splice variants.
Under InSiGHT MMR VCEP v2.0 combination rules (Rule 1): 1 PVS1_VeryStrong criterion is sufficient for Pathogenic classification.
No criteria match.
Met · 3
PVS1 Very strongCanonical splice acceptor variant (IVS2-1G>A, NM_000251.2:c.367-1G>A) disrupting the invariant AG dinucleotide. cDNA analysis from patient blood (Wolf et al., PMID:15926618) confirmed the variant generates a new splice acceptor site 1 bp downstream, resulting in deletion of a guanine (r.367delg) and a frameshift predicted to produce a premature termination codon (p.122fsX173) subject to nonsense-mediated decay. Under InSiGHT MMR VCEP v2.0 PVS1 rules, IVS+/-1 or IVS+/-2 variants where exon skipping or cryptic splice site use disrupts the reading frame and is predicted to undergo NMD qualify for PVS1 at very_strong strength. Confirmed by patient-derived mRNA assay; no additional independent confirmation required as this is a canonical splice site variant. Details ▾Hide ▴
Evidence considered
- Variant at canonical splice acceptor position IVS2-1 (AG→AA)
- SpliceAI max delta score 0.99 (acceptor loss 0.99)
- predicting strong splice disruption
- cDNA analysis from patient lymphocytes confirmed aberrant splicing: new acceptor 1 bp downstream → r.367delg → p.122fsX173 frameshift
- Premature termination codon at codon 173 predicted to trigger NMD (MSH2 NMD boundary at codon 891 per VCEP appendix)
- Variant absent from 100 healthy control alleles in Wolf et al. study
Sources
PM2 SupportingAbsent from gnomAD v2.1 (exomes), gnomAD v4.1, and gnomAD-Canada v1.0. Under InSiGHT MMR VCEP v2.0, PM2_Supporting applies when allele frequency is <0.00002 (<1 in 50,000 alleles) in gnomAD v4. The variant is completely absent from all population databases, satisfying this threshold. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1 (0 alleles observed)
- Absent from gnomAD v4.1 (0 alleles observed)
- Absent from gnomAD-Canada v1.0
- Absent from 100 healthy control alleles in Wolf et al. (PMID:15926618)
Sources
PP5 SupportingExpert panel International Society for Gastrointestinal Hereditary Tumours (InSiGHT) classified as Likely pathogenic. Details ▾Hide ▴
Not met · 12 · evaluated, threshold not reached
PS2 No de novo occurrence data identified in the literature for NM_000251.2:c.367-1G>A. Under VCEP PS2 rules, de novo points require confirmed maternity and paternity in a proband with MMR-deficient LS spectrum tumor. No such reports found. Details ▾Hide ▴
Still missing
- No de novo reports identified in available literature
PS3 Under InSiGHT MMR VCEP v2.0, PS3 requires calibrated functional assay data with defined odds of pathogenicity (as documented in Functional-assay-SVI-documentation-MMR.xlsx) or MMR function defect per the functional assay flowchart. The cDNA splicing analysis by Wolf et al. (PMID:15926618) confirms a splicing aberration at the mRNA level, but this is not a calibrated protein-level functional assay and does not meet VCEP PS3 calibrated assay requirements. The splicing evidence is appropriately captured under PVS1. No calibrated functional assay data available for this variant. Details ▾Hide ▴
Evidence considered
- SVI functional assay documentation reviewed
- no calibrated assay data for c.367-1G>A
- Wolf et al. cDNA splicing data does not constitute a calibrated functional assay per VCEP PS3 specification
Still missing
- No calibrated functional assay (MMR activity
- protein expression
- or monoallelic expression assay) performed for this variant
Sources
vcep_functional_assay_svi_documentation_mmrPMID:15926618 ↗
PP1 No co-segregation data available for NM_000251.2:c.367-1G>A. Under VCEP PP1 rules, co-segregation requires combined Bayes Likelihood Ratio calculations from pedigrees. No such data identified in the literature. Details ▾Hide ▴
Still missing
- No co-segregation data or pedigree analyses available
PP4 Under InSiGHT MMR VCEP v2.0, PP4 requires CRC/endometrial MSI-H tumors with consistent loss of MMR protein expression. No patient phenotype, tumor MSI, or IHC data were available in the case materials. Wolf et al. (PMID:15926618) reported one tumor with MSI-H and one with MSS in the single family carrying this variant, which does not meet PP4 Supporting threshold (1 CRC/endometrial MSI-H tumor). Details ▾Hide ▴
Evidence considered
- Wolf et al. family FH12: one tumor MSI-H
- one tumor MSS
- insufficient for PP4 Supporting (requires at least 1 MSI-H CRC/endometrial tumor per VCEP rules)
Still missing
- No dedicated tumor MSI/IHC data available for independent PP4 assessment
Sources
BA1 Under InSiGHT MMR VCEP v2.0, BA1 requires gnomAD v4 Grpmax filtering allele frequency >=0.001 (0.1%). NM_000251.2:c.367-1G>A is absent from gnomAD v4.1 and does not meet the BA1 threshold. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD v4.1
- allele frequency 0.0
- far below BA1 threshold of >=0.001
Sources
BS1 Under InSiGHT MMR VCEP v2.0, BS1 requires gnomAD v4 Grpmax filtering allele frequency >=0.0001 and <0.001 (0.01-0.1%). NM_000251.2:c.367-1G>A is absent from gnomAD v4.1 and does not meet the BS1 threshold. Details ▾Hide ▴
Evidence considered
- Variant absent from gnomAD v4.1
- allele frequency 0.0
- below BS1 threshold of >=0.0001
Sources
BS2 Under InSiGHT MMR VCEP v2.0, BS2 requires co-occurrence in trans with a known pathogenic variant in the same gene in a CRC patient after age 45 without CMMRD features. No such co-occurrence data identified for NM_000251.2:c.367-1G>A. Details ▾Hide ▴
Still missing
- No in trans co-occurrence data available
BS3 Under InSiGHT MMR VCEP v2.0, BS3 requires calibrated functional assays demonstrating functional odds for pathogenicity <=0.05, or synonymous/intronic variants with no associated mRNA aberration by NMD-inhibited lab assays. The cDNA analysis by Wolf et al. (PMID:15926618) demonstrates the opposite: a confirmed splicing aberration producing a frameshift (r.367delg → p.122fsX173). No calibrated functional assay data supporting normal function exists. BS3 is not met. Details ▾Hide ▴
Evidence considered
- Wolf et al. cDNA analysis confirms splicing aberration
- not normal function
- No calibrated functional assay data showing normal MMR function
Sources
PMID:15926618 ↗vcep_functional_assay_svi_documentation_mmr
BS4 Under InSiGHT MMR VCEP v2.0, BS4 requires formal co-segregation analysis demonstrating lack of co-segregation with disease (Bayes Likelihood Ratio <0.05 for strong, >0.05 and <=0.48 for supporting). No segregation data available for NM_000251.2:c.367-1G>A. Details ▾Hide ▴
Still missing
- No co-segregation analysis available
BP4 Under InSiGHT MMR VCEP v2.0, BP4 Supporting applies to (a) missense variants with HCI prior probability <0.11, or (b) intronic/synonymous variants with SpliceAI delta score <=0.1. NM_000251.2:c.367-1G>A is an intronic variant but SpliceAI predicts strong splice impact (max delta 0.99, acceptor loss 0.99), far exceeding the 0.1 threshold. HCI prior is not applicable for non-missense variants. BP4 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.99 (>0.1 threshold for BP4 Supporting)
- BayesDel score = 0.66 (damaging prediction
- not benign)
- HCI prior not available for intronic variant
Sources
spliceai ↗bayesdel
BP5 Under InSiGHT MMR VCEP v2.0, BP5 requires tumor data demonstrating MSS and/or no loss of MMR protein expression consistent with the variant gene, or BRAF V600E/MLH1 methylation in appropriate tumor context. No tumor phenotype data available for independent BP5 assessment. Details ▾Hide ▴
Still missing
- No tumor MSI
- IHC
- BRAF
- or MLH1 methylation data available
BP7 Under InSiGHT MMR VCEP v2.0, BP7 applies to synonymous or intronic variants at or beyond position -21 (3' splice site) or +7 (5' splice site) from the exon boundary. NM_000251.2:c.367-1G>A is at position -1 of the splice acceptor site of intron 2, which is within the canonical splice consensus region. The -1 position is a universally conserved splice dinucleotide, not a deep intronic variant eligible for BP7. Details ▾Hide ▴
Evidence considered
- Variant is at IVS2-1 (splice acceptor -1 position)
- within the invariant AG dinucleotide
- Position -1 is not at or beyond -21 from the exon boundary
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 under InSiGHT MMR VCEP v2.0 applies to (a) missense substitutions encoding the same amino acid change as a known pathogenic variant, or (b) variants affecting the same non-canonical splice nucleotide as a confirmed pathogenic splice variant. This variant is a canonical splice site change (IVS-1), not a missense or non-canonical splice variant. PS1 is not applicable. Details ▾Hide ▴
No further detail was recorded.
PS4 VCEPPS4 is not applicable under the InSiGHT MMR VCEP v2.0 framework for MSH2. Details ▾Hide ▴
No further detail was recorded.
PM1 VCEPPM1 is designated as Not Applicable by the InSiGHT MMR VCEP v2.0 for MSH2. Domain-level criteria are not applied under this VCEP framework. Details ▾Hide ▴
No further detail was recorded.
PM5 N/APM5 under InSiGHT MMR VCEP v2.0 applies only to missense changes at an amino acid residue where a different missense change was classified as Pathogenic or Likely Pathogenic. NM_000251.2:c.367-1G>A is a canonical splice site variant, not a missense change. PM5 is not applicable. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPPM6 is designated as Not Applicable by the InSiGHT MMR VCEP v2.0. De novo evidence for MMR genes is assessed through the PS2 points system instead. Details ▾Hide ▴
No further detail was recorded.
PP2 VCEPPP2 is designated as Not Applicable by the InSiGHT MMR VCEP v2.0. Details ▾Hide ▴
No further detail was recorded.
PP3 N/AUnder InSiGHT MMR VCEP v2.0, PP3 applies to (a) missense variants with HCI prior probability >0.68, or (b) predicted splice defects for non-canonical splice nucleotides using SpliceAI delta score >=0.2. NM_000251.2:c.367-1G>A is a canonical splice site variant (IVS-1), not a missense or non-canonical splice variant. The VCEP PVS1 rules explicitly state that PP3 must not be combined with PVS1 for IVS+/-1 or IVS+/-2 variants. The splice prediction evidence is captured under PVS1. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.99 (strong splice disruption prediction)
- HCI prior not applicable (intronic variant
- not missense)
- VCEP PVS1 rule prohibits combining PVS1 with PP3 for canonical splice variants
Sources
spliceai ↗vcep_hci_priors_msh2
BP1 VCEPBP1 is designated as Not Applicable by the InSiGHT MMR VCEP v2.0. Details ▾Hide ▴
No further detail was recorded.
BP2 VCEPBP2 is designated as Not Applicable by the InSiGHT MMR VCEP v2.0; BS2 is used instead. Details ▾Hide ▴
No further detail was recorded.
BP3 VCEPIn-frame deletions/insertions in repetitive regions without known function; not applicable to a canonical splice site substitution. Details ▾Hide ▴
No further detail was recorded.
BP6 VCEPBP6 is designated as Not Applicable by the InSiGHT MMR VCEP v2.0. The VCEP explicitly states this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
No further detail was recorded.
PS5 N/APS5 is not defined in the InSiGHT MMR VCEP v2.0 criteria set for MSH2. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- MSH2
- Transcript
- NM_000251.2
- Coding (HGVS c.)
- NM_000251.2:c.367-1G>A
- Protein (HGVS p.)
- NP_000242.1:p.?
- GRCh38
- chr2:47410093 G>A
- GRCh37
- chr2:47637232 G>A
- ClinVar
- 91075
Gene diagram
Every interpreted variant in MSH2, mapped onto the exon structure of NM_000251.2. Select a row to find it on the plot.
MSH2NM_000251.2
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
- 0.660
How the predictions were used
BP4 Under InSiGHT MMR VCEP v2.0, BP4 Supporting applies to (a) missense variants with HCI prior probability <0.11, or (b) intronic/synonymous variants with SpliceAI delta score <=0.1. NM_000251.2:c.367-1G>A is an intronic variant but SpliceAI predicts strong splice impact (max delta 0.99, acceptor loss 0.99), far exceeding the 0.1 threshold. HCI prior is not applicable for non-missense variants. BP4 is not met. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.99 (>0.1 threshold for BP4 Supporting)
- BayesDel score = 0.66 (damaging prediction
- not benign)
- HCI prior not available for intronic variant
Sources
spliceai ↗bayesdel
BP7 Under InSiGHT MMR VCEP v2.0, BP7 applies to synonymous or intronic variants at or beyond position -21 (3' splice site) or +7 (5' splice site) from the exon boundary. NM_000251.2:c.367-1G>A is at position -1 of the splice acceptor site of intron 2, which is within the canonical splice consensus region. The -1 position is a universally conserved splice dinucleotide, not a deep intronic variant eligible for BP7. Details ▾Hide ▴
Evidence considered
- Variant is at IVS2-1 (splice acceptor -1 position)
- within the invariant AG dinucleotide
- Position -1 is not at or beyond -21 from the exon boundary
PP3 N/AUnder InSiGHT MMR VCEP v2.0, PP3 applies to (a) missense variants with HCI prior probability >0.68, or (b) predicted splice defects for non-canonical splice nucleotides using SpliceAI delta score >=0.2. NM_000251.2:c.367-1G>A is a canonical splice site variant (IVS-1), not a missense or non-canonical splice variant. The VCEP PVS1 rules explicitly state that PP3 must not be combined with PVS1 for IVS+/-1 or IVS+/-2 variants. The splice prediction evidence is captured under PVS1. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.99 (strong splice disruption prediction)
- HCI prior not applicable (intronic variant
- not missense)
- VCEP PVS1 rule prohibits combining PVS1 with PP3 for canonical splice variants
Sources
spliceai ↗vcep_hci_priors_msh2
Statement
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.99). BayesDel score = 0.66.
8 paper records listed. 1 cited in the classification.
Cited in the classification
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PMID 15926618 ↗Spectrum of germ-line MLH1 and MSH2 mutations in Austrian patients with hereditary nonpolyposis colorectal cancer.Wolf B et al. · 2005 AprNM_000251.2:c.367-1G>A was identified in an Austrian HNPCC family (FH12) fulfilling Amsterdam criteria. cDNA analysis from patient lymphocytes demonstrated that the variant in the invariant splice acceptor site of MSH2 exon 3 generates a new splice acceptor site 1 bp downstream, resulting in deletion of a guanine (r.367delg) and a frameshift mutation (p.Ile122fsTer173) leading to a premature termination codon. The variant was absent from 100 healthy control alleles.→ PVS1 → PM2 Names this variant
Source detail
cDNA analysis revealed that the substitution MSH2, c.367-1G > A in the invariant splice acceptor site of exon 3 generated a new splice acceptor site 1 bp downstream and resulted in a frameshift mutation due to deletion of a G.
Location Results, paragraph describing splice site variants; Table 4 (MSH2 variants); cDNA analysis methods
Context cDNA synthesized from patient peripheral blood lymphocyte RNA; RT-PCR and Sanger sequencing
Other recorded publications
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PMID 15849733 ↗Spectrum and frequencies of mutations in MSH2 and MLH1 identified in 1,721 German families suspected of hereditary nonpolyposis colorectal cancer.Mangold E et al. · 2005Large German HNPCC cohort study (1,721 families) describing MSH2 and MLH1 mutation spectrum and frequencies. NM_000251.2:c.367-1G>A was not identified among the reported pathogenic mutations or unclassified variants in this study.Does not name this variant
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PMID 16199547 ↗Splicing in action: assessing disease causing sequence changes.Baralle D et al. · 2005Review article on the impact of sequence variants on pre-mRNA splicing, covering splice site mutations, splicing regulatory elements, and methods for assessing splicing defects. NM_000251.2:c.367-1G>A is not specifically discussed.Does not name this variant
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PMID 24362816 ↗Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.Thompson BA et al. · 2014Describes the development and application of the InSiGHT 5-tiered classification scheme for 2,360 unique MMR gene variants. NM_000251.2:c.367-1G>A was not explicitly identified in the full-text search of this methodology paper.Does not name this variant
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PMID 20301390 ↗Lynch Syndrome.Adam MP et al. · 1993GeneReviews chapter on Lynch Syndrome providing clinical description, diagnosis, and management recommendations. NM_000251.2:c.367-1G>A is not specifically discussed in this general reference.Does not name this variant
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PMID 24310308 ↗ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, familial adenomatous polyposis, and MYH-associated polyposis).ACMG technical standards and guidelines for genetic testing for inherited colorectal cancer (Lynch syndrome, FAP, MAP). Provides testing algorithms and technical specifications but does not discuss individual variants including NM_000251.2:c.367-1G>A.Does not name this variant
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PMID 25394175 ↗A practice guideline from the American College of Medical Genetics and Genomics and the National Society of Genetic Counselors: referral indications for cancer predisposition assessment.Hampel H et al. · 2015ACMG/NSGC practice guideline on referral indications for cancer predisposition assessment. Provides criteria for when to refer patients for cancer genetic consultation. Does not discuss individual gene variants.Does not name this variant
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PMID 25452455 ↗Hereditary colorectal cancer syndromes: American Society of Clinical Oncology Clinical Practice Guideline endorsement of the familial risk-colorectal cancer: European Society for Medical Oncology Clinical Practice Guidelines.ASCO endorsement of ESMO clinical practice guidelines for familial risk-colorectal cancer. Provides recommendations on screening, surveillance, and management for hereditary CRC syndromes. Does not discuss individual gene variants.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 0.990
Open source ↗
ClinVar
2 Likely pathogenic · 1 Pathogenic
Open source ↗
COSMIC
Captured COSMIC 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/91075/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-47637232-G-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-47410093-G-A?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-47410093-G-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000251.2%3Ac.367-…
- OncoKB ↗www.oncokb.org/gene/MSH2/?
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MSH2+c.367-1G%3EA
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 Likely pathogenic (2 clinical laboratories) and as Pathogenic (1 clinical laboratory) and as Likely pathogenic by International Society for Gastrointestinal Hereditary Tumours (InSiGHT) (expert panel). (ClinVarID = 91075)
In silico
SpliceAI predicts possible splice impact for this variant (max delta score = 0.99). BayesDel score = 0.66.
Somatic
This variant has not previously been reported in somatic cancers (COSMIC).