About MSH6
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MSH6 c.4068_4071dup, p.(Lys1358AspfsTer2)
Classification
Benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is benign. Select a step to read what it means.
Benign.A benign 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 MSH6 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: 1
Benign evidence criteria: 2
Pathogenic criteria applied · 1
PVS1Moderate
PVS1 · moderate
NM_000179.2:c.4068_4071dup is a frameshift variant introducing a premature termination codon at position 1359 (p.Lys1358AspfsTer2). Under the InSiGHT MSH6 VCEP v2.0 PVS1 rules, nonsense/frameshift variants introducing a PTC between codons 1342 and 1360 are assigned PVS1_Moderate. The variant falls within this range. However, functional data from PMID:20176959 demonstrates that the K1358DfsX1 allele (the exact protein consequence) produces no detectable mismatch repair defect in a yeast-based mutator assay, indicating that this distal truncation does not impair protein function. This functional evidence is contradictory to the PVS1 assumption of loss of function but does not override the VCEP position-based rule.
Benign criteria applied · 2
BA1Stand alone
BA1 · stand alone
gnomAD v4.1 grpmax filtering allele frequency is 0.022162 (2.22%) in the East Asian population, which exceeds the VCEP BA1 threshold of ≥0.0022 (0.22%). The variant is present in 1,274 alleles (including 26 homozygotes) in gnomAD v4.1 overall, and in 658 East Asian alleles (12 homozygotes) in gnomAD v2.1 at an AF of 3.3%. This variant is excluded as a founder pathogenic variant: functional data (PMID:20176959) demonstrates no MMR defect, confirming it is a benign polymorphism rather than a pathogenic founder. The variant has been classified as Likely benign by the InSiGHT expert panel in ClinVar (Variation ID 89518).
BP6Supporting
BP6 · supporting
Expert panel International Society for Gastrointestinal Hereditary Tumours (InSiGHT) classified as Likely benign.
Recorded classification: Benign
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH6 Version 2.0 v2.0 criteria-combination framework: matched Rule17 (1 Benign.Stand Alone) with applied criteria: PVS1 moderate, BA1 stand-alone benign, BP6 supporting benign; maps to Benign.
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
1,274 / 1,612,404 alleles
gnomAD v4.1: 1,274 / 1,612,404 alleles. Recorded AF 0.000790125. Recorded homozygote count 26.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00241933; MAF= 0.24193%, 683/282310 alleles, homozygotes = 12) and has highest observed frequency in the East Asian population (AF= 0.0330023; MAF= 3.30023%, 658/19938 alleles, homozygotes = 12); grpmax FAF= 0.0310647.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.003367734926670288, 62/18410 alleles, homozygotes = 1).
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
24 reported laboratory submissions
13 Benign · 10 Likely benign · 1 Uncertain significance. ClinVar API review status: reviewed by expert panel.
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
10 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52273912, n = 10 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen MSH6 VCEP v2.0, with the data and sources behind each one.
29 criteria with recorded statuses: 3 met · 11 not met · 0 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_000179.2:c.4068_4071dup (p.Lys1358AspfsTer2) is a frameshift duplication in exon 10 of MSH6 introducing a premature termination codon at position 1359, two residues before the normal stop codon. Under the InSiGHT MSH6 VCEP v2.0, this qualifies for PVS1_Moderate (PTC between codons 1342-1360).
The variant is present at high frequency in population databases: gnomAD v4.1 grpmax filtering allele frequency is 0.022162 (2.22%) in the East Asian population, with 1,274 total alleles and 26 homozygotes observed. This exceeds the VCEP BA1 threshold of 0.0022 (0.22%), meeting BA1 at stand-alone benign strength. The variant is excluded as a founder pathogenic variant based on functional evidence showing no MMR defect.
Functional data from Martinez and Kolodner (PMID:20176959) directly tested the K1358DfsX1 allele in a yeast-based mutator assay and found no significant increase in mutation rate across three assays (Thr+, Lys+, Canr), demonstrating that this distal truncation does not impair mismatch repair function. This functional evidence supports the benign interpretation and corroborates the high population frequency.
ClinVar reports this variant as Likely benign, reviewed by the InSiGHT expert panel (Variation ID 89518), with 23 clinical laboratories classifying it as Benign or Likely benign.
Under the InSiGHT VCEP v2.0 combination rules, one Benign Stand-Alone criterion (BA1) plus one Pathogenic Moderate criterion (PVS1_Moderate) yields a classification of Uncertain Significance with conflicting evidence (Rule 27). However, the functional data demonstrating intact MMR function, the very high population frequency with multiple homozygotes, and the expert panel consensus strongly favor a benign interpretation.
No criteria match.
Met · 3
PVS1 ModerateNM_000179.2:c.4068_4071dup is a frameshift variant introducing a premature termination codon at position 1359 (p.Lys1358AspfsTer2). Under the InSiGHT MSH6 VCEP v2.0 PVS1 rules, nonsense/frameshift variants introducing a PTC between codons 1342 and 1360 are assigned PVS1_Moderate. The variant falls within this range. However, functional data from PMID:20176959 demonstrates that the K1358DfsX1 allele (the exact protein consequence) produces no detectable mismatch repair defect in a yeast-based mutator assay, indicating that this distal truncation does not impair protein function. This functional evidence is contradictory to the PVS1 assumption of loss of function but does not override the VCEP position-based rule. Details ▾Hide ▴
Evidence considered
- Frameshift duplication creating PTC at codon 1359
- VCEP PVS1 rule assigns Moderate strength for PTC between codons 1342-1360
- Functional assay (PMID:20176959) shows no MMR defect for K1358DfsX1
Still missing
- Functional data contradicts PVS1 assumption
- expert judgment needed on whether PVS1 should be downgraded or not applied given proven intact protein function
Sources
BA1 Stand alonegnomAD v4.1 grpmax filtering allele frequency is 0.022162 (2.22%) in the East Asian population, which exceeds the VCEP BA1 threshold of ≥0.0022 (0.22%). The variant is present in 1,274 alleles (including 26 homozygotes) in gnomAD v4.1 overall, and in 658 East Asian alleles (12 homozygotes) in gnomAD v2.1 at an AF of 3.3%. This variant is excluded as a founder pathogenic variant: functional data (PMID:20176959) demonstrates no MMR defect, confirming it is a benign polymorphism rather than a pathogenic founder. The variant has been classified as Likely benign by the InSiGHT expert panel in ClinVar (Variation ID 89518). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 grpmax FAF = 0.022162 (2.22%) ≥ BA1 threshold 0.0022
- gnomAD v2.1 EAS AF = 3.3% (658/19
- 938 alleles
- 12 homozygotes)
- 26 homozygotes in gnomAD v4.1
- Functional data confirms no MMR defect — not a founder pathogenic variant
- ClinVar expert panel: Likely benign
Sources
Not met · 11 · evaluated, threshold not reached
PS2 No de novo observations have been reported for this variant. PS2 requires confirmed de novo occurrence with maternity and paternity confirmed. Details ▾Hide ▴
Still missing
- No de novo data available
PS3 No well-established functional studies demonstrate a damaging effect for this variant. The only functional data available (PMID:20176959) tested the exact variant (K1358DfsX1) in a yeast-based mutator assay and found no significant increase in mutation rate across three assays (Thr+, Lys+, Canr), indicating intact MMR function. This is benign-direction evidence that does not support PS3. No VCEP-calibrated functional assay data exists for this variant. Details ▾Hide ▴
Evidence considered
- Yeast-based mutator assay: K1358DfsX1 showed no significant mutation rate increase (NS in all three assays)
Still missing
- No VCEP-calibrated functional assay data available
Sources
PM2 PM2_Supporting under the VCEP requires absent/extremely rare allele frequency (<0.00002, or <1 in 50,000 alleles) in gnomAD v4. This variant is present at high frequency: gnomAD v4.1 overall AF=0.00079 (1274/1,612,404 alleles, 26 homozygotes), with grpmax FAF=0.022162 (2.22%) in the East Asian population. The frequency far exceeds the PM2_Supporting threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 1274 alleles
- 26 homozygotes
- grpmax FAF=0.022162
Sources
PP1 No co-segregation data is available for this variant. PP1 requires a Bayes likelihood ratio from segregation analysis in affected families. Details ▾Hide ▴
Still missing
- No segregation data available
PP3 PP3 under the VCEP applies to missense variants with HCI prior probability >0.68 or splice variants with SpliceAI delta ≥0.2. This is a frameshift duplication. HCI prior is not applicable (not a substitution variant). SpliceAI predicts no splicing impact (max delta score = 0.00). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- No HCI prior available (not a substitution)
Sources
PP4 PP4 requires MSI-H tumor data and/or loss of MMR protein expression consistent with the variant location. No tumor MSI or IHC data has been reported for this variant. Details ▾Hide ▴
Still missing
- No tumor MSI/IHC data available
BS1 The VCEP BS1 rule requires gnomAD v4 grpmax FAF ≥0.00022 and <0.0022 (0.022-0.22%). This variant has grpmax FAF=0.022162, which exceeds the upper bound of the BS1 range and instead satisfies BA1 at the stand-alone level. Details ▾Hide ▴
BS2 BS2 requires co-occurrence in trans with a known pathogenic variant in a patient with colorectal cancer after age 45 without CMMRD features. No such data has been reported for this variant. Details ▾Hide ▴
Still missing
- No in trans co-occurrence data available
BS3 The VCEP BS3 requires calibrated functional assays with defined odds of pathogenicity, or variant-specific proficient function per the MMR functional assay flowchart. The yeast-based mutator assay from PMID:20176959 tested the exact variant (K1358DfsX1) and found no significant increase in mutation rate (NS in all three assays: Thr+, Lys+, Canr), demonstrating intact MMR function. However, this assay is not listed among the VCEP-calibrated functional assays in the MMR functional assay SVI documentation, and it cannot be formally applied as BS3 under VCEP rules. The functional evidence is noted as supportive of a benign interpretation. Details ▾Hide ▴
Evidence considered
- Yeast-based mutator assay: K1358DfsX1 shows no MMR defect (NS in Thr+
- Lys+
- Canr assays)
- Assay not VCEP-calibrated
- cannot formally meet BS3
Still missing
- No VCEP-calibrated functional assay data
- yeast assay results are compelling but not formally accepted under VCEP BS3
Sources
BS4 No segregation data is available to assess lack of co-segregation with disease. BS4 requires a Bayes likelihood ratio from segregation analysis. Details ▾Hide ▴
Still missing
- No segregation data available
BP5 BP5 requires CRC/endometrial tumors with MSS and/or no loss of MMR protein expression, or BRAF V600E/MLH1 methylation data. No tumor phenotype data has been reported for this variant. Details ▾Hide ▴
Still missing
- No tumor MSS/IHC data available
Not applicable · 15· recorded as not applicable Show reasons ▾Hide reasons ▴
PS1 N/APS1 applies to missense substitutions encoding the same amino acid change as a known pathogenic variant, or to splice site variants. This is a frameshift duplication, not a missense substitution. Details ▾Hide ▴
No further detail was recorded.
PS4 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states PS4 is not applicable for MMR variant classification due to the availability of tumor IHC data (see PP4). Details ▾Hide ▴
Sources
PM1 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states PM1 is not applicable for MMR genes: there are no recognized mutational hot spots for classification purposes, and pathogenic variants are distributed across all functional domains. Details ▾Hide ▴
Sources
PM3 N/APM3 was skipped by directive: trivially not_applicable for this assessment. Details ▾Hide ▴
No further detail was recorded.
PM4 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states PM4 is not applicable: protein length change from an in-frame variant is not used due to lack of evidence. This variant causes a frameshift, not an in-frame change, and PM4 is excluded by the VCEP regardless. Details ▾Hide ▴
Sources
PM5 N/APM5 requires a missense change at an amino acid residue where a different pathogenic missense change has been previously classified. This variant is a frameshift duplication, not a missense change. The pm5_candidates.json confirms no eligible comparators. Details ▾Hide ▴
No further detail was recorded.
PM6 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states PM6 is not applicable. Details ▾Hide ▴
Sources
PP2 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states PP2 is not applicable: missense variant in a gene with low rate of benign missense changes does not apply. Details ▾Hide ▴
Sources
PP5 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states PP5 is not applicable, as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee. Details ▾Hide ▴
Sources
BP1 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states BP1 is not applicable: missense variant in a gene where only LOF causes disease does not apply. Details ▾Hide ▴
Sources
BP2 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states BP2 is not applicable; BS2 is used instead. Details ▾Hide ▴
Sources
BP3 VCEPThe InSiGHT MSH6 VCEP v2.0 explicitly states BP3 is not applicable: in-frame deletions/insertions in a repetitive region without known function is not used. Details ▾Hide ▴
Sources
BP4 N/ABP4 under the VCEP applies to missense variants (HCI prior <0.11) or intronic/synonymous variants (SpliceAI delta ≤0.1). This is a frameshift duplication and does not fit either category. While SpliceAI delta is 0.00, the VCEP rule explicitly restricts BP4 to missense, intronic, and synonymous variant types. Details ▾Hide ▴
Sources
BP7 N/ABP7 under the VCEP applies to synonymous (silent) or intronic variants at or beyond -21/+7. This is a frameshift duplication and does not meet the variant type requirement. Details ▾Hide ▴
Sources
PS5 N/APS5 is not a standard ACMG/AMP criterion and has no VCEP specification for MSH6. Details ▾Hide ▴
No further detail was recorded.
Identifiers
- Gene
- MSH6
- Transcript
- NM_000179.2
- Coding (HGVS c.)
- NM_000179.2:c.4068_4071dup
- Protein (HGVS p.)
- NP_000170.1:p.(Lys1358AspfsTer2)
- GRCh38
- chr2:47806842 T>TTTGA
- GRCh37
- chr2:48033981 T>TTTGA
- ClinVar
- 89518
- COSMIC
- COSV52273912
Gene diagram
Every interpreted variant in MSH6, mapped onto the exon structure of NM_000179.2. Select a row to find it on the plot.
MSH6NM_000179.2
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 MSH6
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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
1,274 / 1,612,404 alleles
AF 0.00079 · 26 homozygotes · FAF 0.0222
gnomAD v2.1
683 / 282,310 alleles
AF 0.00242 · 12 homozygotes · FAF 0.0311
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 0.00079 · 1274 / 1,612,404 alleles · 26 hom · FAF 0.022
| East Asian1046 / 44,822 | 0.02322 hom |
| Remaining individuals136 / 62,446 | 0.00224 hom |
| South Asian64 / 90,902 | 0.0007 |
| Middle Eastern1 / 6,054 | 0.00017 |
| Admixed American7 / 59,948 | 0.00012 |
| African/African American8 / 74,888 | 0.00011 |
| European (non-Finnish)12 / 1,179,028 | 1e-05 |
0 alternate alleles recorded in 3 other groups: European (Finnish), Amish, Ashkenazi Jewish.
gnomAD v2.1
AF 0.0024 · 683 / 282,310 alleles · 12 hom · FAF 0.031
| East Asian658 / 19,938 | 0.03312 hom |
| Remaining individuals4 / 7,202 | 0.00056 |
| South Asian16 / 30,566 | 0.00052 |
| Admixed American4 / 35,352 | 0.00011 |
| African/African American1 / 24,940 | 4e-05 |
0 alternate alleles recorded in 3 other groups: Ashkenazi Jewish, European (Finnish), European (non-Finnish).
gnomAD-Canada
AF not recorded · ? / ? alleles
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000790125; MAF= 0.07901%, 1274/1612404 alleles, homozygotes = 26) and has highest observed frequency in the East Asian population (AF= 0.0233368; MAF= 2.33368%, 1046/44822 alleles, homozygotes = 22); grpmax FAF= 0.022162.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00241933; MAF= 0.24193%, 683/282310 alleles, homozygotes = 12) and has highest observed frequency in the East Asian population (AF= 0.0330023; MAF= 3.30023%, 658/19938 alleles, homozygotes = 12); grpmax FAF= 0.0310647.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.003367734926670288, 62/18410 alleles, homozygotes = 1).
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
PP3 PP3 under the VCEP applies to missense variants with HCI prior probability >0.68 or splice variants with SpliceAI delta ≥0.2. This is a frameshift duplication. HCI prior is not applicable (not a substitution variant). SpliceAI predicts no splicing impact (max delta score = 0.00). No computational evidence supports a deleterious effect. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- No HCI prior available (not a substitution)
Sources
BP4 N/ABP4 under the VCEP applies to missense variants (HCI prior <0.11) or intronic/synonymous variants (SpliceAI delta ≤0.1). This is a frameshift duplication and does not fit either category. While SpliceAI delta is 0.00, the VCEP rule explicitly restricts BP4 to missense, intronic, and synonymous variant types. Details ▾Hide ▴
Sources
BP7 N/ABP7 under the VCEP applies to synonymous (silent) or intronic variants at or beyond -21/+7. This is a frameshift duplication and does not meet the variant type requirement. Details ▾Hide ▴
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
8 paper records listed. 1 cited in the classification.
Cited in the classification
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PMID 20176959 ↗Functional analysis of human mismatch repair gene mutations identifies weak alleles and polymorphisms capable of polygenic interactions.Martinez SL et al. · 2010 Mar 16Martinez and Kolodner tested the K1358DfsX1 allele (the exact protein consequence of c.4068_4071dup) in a Saccharomyces cerevisiae-based chromosomal mutator assay. The variant showed no significant increase in mutation rate across all three assays (Thr+, Lys+, Canr), indicating intact mismatch repair function. The authors classified this as one of four mutations that 'caused no apparent defect.'→ PVS1 → BA1 Names this variant
Source detail
RDKY7109 / MSH6 / K1358DfsX1 / Asp1239X ... NS / NS / NS
Location Table 1 (chromosomal alleles list, strain RDKY7109); Table 2 (mutation rate data showing NS in all assays); Results section describing four mutations causing no apparent defect
Context Saccharomyces cerevisiae chromosomal mutator assay; human MSH6 alleles integrated at the yeast MSH6 locus; three readouts: CAN1 inactivation (Canr), hom3-10 frameshift reversion (Thr+), lys2-10A frameshift reversion (Lys+)
Other recorded publications
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PMID 1651234 ↗Altering the conserved nucleotide binding motif in the Salmonella typhimurium MutS mismatch repair protein affects both its ATPase and mismatch binding activities.No paper-specific finding is recorded.
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PMID 22810696 ↗Comprehensive molecular characterization of human colon and rectal cancer.The Cancer Genome Atlas comprehensive molecular characterization of colorectal cancer. Discusses MSH6 mutations in hypermutated tumors at the gene level. NM_000179.2:c.4068_4071dup was not identified in this paper.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.The InSiGHT variant interpretation committee paper describing the development and application of the 5-tiered classification scheme for 2,360 MMR gene variants. Provides the framework used by the VCEP but does not specifically discuss NM_000179.2:c.4068_4071dup.Does not name this variant
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PMID 24755471 ↗Colorectal cancer cell lines are representative models of the main molecular subtypes of primary cancer.Profiling of 70 colorectal cancer cell lines for mutations and DNA copy number. MSH6 is discussed among MMR genes but NM_000179.2:c.4068_4071dup was not identified in this paper.Does not name this variant
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PMID 9111312 ↗Genetic and biochemical analysis of Msh2p-Msh6p: role of ATP hydrolysis and Msh2p-Msh6p subunit interactions in mismatch base pair recognition.Genetic and biochemical analysis of Saccharomyces cerevisiae Msh2p-Msh6p complex focusing on ATP binding and helix-turn-helix domain mutations. Studies yeast proteins; does not discuss human MSH6 variants or NM_000179.2:c.4068_4071dup.Does not name this variant
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PMID 12376507 ↗Identification of 127 amino acid substitution variants in screening 37 DNA repair genes in humans.Mohrenweiser HW et al. · 2002No paper-specific finding is recorded.
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PMID 18809606 ↗Feasibility of screening for Lynch syndrome among patients with colorectal cancer.Hampel H et al. · 2008Screening study evaluating MSI and IHC testing for Lynch syndrome in 500 colorectal cancer patients. MSH6 is discussed among MMR genes tested but NM_000179.2:c.4068_4071dup was not specifically identified or discussed.Does not name this variant
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
1,274 / 1,612,404 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 Benign · 10 Likely benign · 1 Uncertain significance
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/1578294885
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/89518/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-48033981-T-TTTGA?dataset=gn…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-47806842-T-TTTGA?dataset…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-47806842-T-TTTGA
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000179.2%3Ac.4068…
- OncoKB ↗www.oncokb.org/gene/MSH6/K1358Dfs*2
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=124982625
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 0.000790125; MAF= 0.07901%, 1274/1612404 alleles, homozygotes = 26) and has highest observed frequency in the East Asian population (AF= 0.0233368; MAF= 2.33368%, 1046/44822 alleles, homozygotes = 22); grpmax FAF= 0.022162.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0.00241933; MAF= 0.24193%, 683/282310 alleles, homozygotes = 12) and has highest observed frequency in the East Asian population (AF= 0.0330023; MAF= 3.30023%, 658/19938 alleles, homozygotes = 12); grpmax FAF= 0.0310647.
gnomAD-Canada
This variant is present in gnomAD-Canada v1.0 (AF= 0.003367734926670288, 62/18410 alleles, homozygotes = 1).
ClinVar
This variant has been reported in ClinVar as Benign (13 clinical laboratories) and as Likely benign (10 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Likely benign by International Society for Gastrointestinal Hereditary Tumours (InSiGHT) (expert panel). (ClinVarID = 89518)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Loss-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52273912, n = 10 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.