About MSH6
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
MSH6 c.2526T>G, p.(Ala842=)
Classification
Likely benign
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely benign. Select a step to read what it means.
Likely benign.A likely 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 v2.0.0. 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
PM2Supporting
PM2 · supporting
c.2526T>G is extremely rare in population databases. In gnomAD v4.1 the overall allele frequency is 8.06×10⁻⁶ (13/1,613,006 alleles, 0 homozygotes), which is below the VCEP MSH6 PM2_Supporting threshold of <0.00002 (<1 in 50,000 alleles). The variant is also rare in gnomAD v2.1 (AF=3.62×10⁻⁵, 9/248,608 alleles).
Benign criteria applied · 2
BP4Supporting
BP4 · supporting
SpliceAI predicts no splicing impact for this synonymous variant (max delta score = 0.00, ≤0.1). Per the VCEP MSH6 BP4_Supporting rule, synonymous variants with SpliceAI delta score ≤0.1 meet BP4_Supporting.
BP7Supporting
BP7 · supporting
c.2526T>G is a synonymous (silent) variant located at coding position 2526 in exon 4 (c.628-3172), well within the exon interior and far from canonical splice sites. Per VCEP MSH6 BP7, synonymous variants at or beyond the -21/+7 splice region meet BP7_Supporting. Variants may satisfy both BP7 and BP4 per VCEP rules.
Recorded classification: Likely benign
ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for MSH6 Version 2.0.0 v2.0.0 criteria-combination framework: matched Rule19 (Benign.Supporting >=2) with applied criteria: PM2 supporting, BP4 supporting, BP7 supporting; maps to Likely 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
13 / 1,613,006 alleles
gnomAD v4.1: 13 / 1,613,006 alleles. Recorded AF 8.05949e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.62016e-05; MAF= 0.00362%, 9/248608 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000490838; MAF= 0.04908%, 9/18336 alleles, homozygotes = 0); grpmax FAF= 0.00025523.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
7 reported laboratory submissions
5 Likely benign · 1 Likely Benign · 1 Benign. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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 MSH6 VCEP v2.0.0, with the data and sources behind each one.
26 criteria with recorded statuses: 3 met · 11 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
c.2526T>G (p.Ala842=) is a synonymous variant in MSH6 exon 4 with no predicted effect on splicing (SpliceAI max delta = 0.00).
The variant is extremely rare in population databases, with an overall allele frequency of 8.06×10⁻⁶ in gnomAD v4.1 (13/1,613,006 alleles, 0 homozygotes), meeting PM2_Supporting per VCEP MSH6 (threshold <0.00002).
As a synonymous variant with no predicted splicing impact (SpliceAI delta = 0.00), BP4_Supporting is met per VCEP MSH6 rule for synonymous variants with SpliceAI delta ≤0.1.
The variant is a synonymous substitution located deep within exon 4 (c.628-3172), far from splice junctions, meeting BP7_Supporting per VCEP MSH6 rule for synonymous variants at or beyond -21/+7 position.
This variant has been reported in ClinVar as Likely benign by 5 clinical laboratories, Likely Benign by 1, and Benign by 1 (ClinVar ID: 186376, review status: criteria provided, single submitter). However, BP6 is not applicable per VCEP rules.
No functional studies, segregation data, tumor phenotype data, or de novo observations have been reported for this variant. No publications mention NM_000179.3:c.2526T>G specifically.
No criteria match.
Met · 3
PM2 Supportingc.2526T>G is extremely rare in population databases. In gnomAD v4.1 the overall allele frequency is 8.06×10⁻⁶ (13/1,613,006 alleles, 0 homozygotes), which is below the VCEP MSH6 PM2_Supporting threshold of <0.00002 (<1 in 50,000 alleles). The variant is also rare in gnomAD v2.1 (AF=3.62×10⁻⁵, 9/248,608 alleles). Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 overall AF = 8.06×10⁻⁶
- below VCEP PM2 threshold of <2×10⁻⁵. gnomAD v2.1 AF = 3.62×10⁻⁵. Highest subpopulation frequency in East Asian (v4: AF=2.67×10⁻⁴
- v2: AF=4.91×10⁻⁴).
Sources
BP4 SupportingSpliceAI predicts no splicing impact for this synonymous variant (max delta score = 0.00, ≤0.1). Per the VCEP MSH6 BP4_Supporting rule, synonymous variants with SpliceAI delta score ≤0.1 meet BP4_Supporting. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- well below the BP4_Supporting threshold of ≤0.1 for synonymous variants. REVEL and BayesDel are not applicable (synonymous variant). HCI prior not found.
Sources
BP7 Supportingc.2526T>G is a synonymous (silent) variant located at coding position 2526 in exon 4 (c.628-3172), well within the exon interior and far from canonical splice sites. Per VCEP MSH6 BP7, synonymous variants at or beyond the -21/+7 splice region meet BP7_Supporting. Variants may satisfy both BP7 and BP4 per VCEP rules. Details ▾Hide ▴
Evidence considered
- Synonymous variant at c.2526 in exon 4 (spanning c.628-3172)
- far from exon-intron boundaries. SpliceAI confirms no predicted splice impact (delta=0.00).
Sources
Not met · 11 · evaluated, threshold not reached
PS2 No de novo observations have been reported for this variant. VCEP MSH6 PS2 requires de novo points from confirmed parentage testing; no such data are available. Details ▾Hide ▴
Evidence considered
- No de novo data identified in ClinVar
- literature
- or evidence sources.
Still missing
- No de novo testing data available.
PS3 No variant-specific functional data are available for c.2526T>G. OncoKB reports no curated functional evidence. The VCEP functional assay documentation does not include this variant. No calibrated functional odds for pathogenicity can be assessed. Details ▾Hide ▴
Evidence considered
- No functional assay data available for this synonymous variant
- OncoKB classification is 'Unknown Oncogenic Effect' with no associated PMIDs.
Still missing
- No functional studies have been performed on this variant.
Sources
PP1 No co-segregation data are available for this variant. VCEP MSH6 PP1 requires co-segregation with disease in pedigrees with a combined Bayes Likelihood Ratio exceeding defined thresholds; no such data have been reported. Details ▾Hide ▴
Evidence considered
- No co-segregation or pedigree data identified.
Still missing
- No family segregation studies available.
PP3 VCEP MSH6 PP3 criteria do not apply to this variant. The HCI prior lookup for c.2526T>G returned no result (variant not in the MSH6 HCI priors table). The SpliceAI-based PP3 rule (delta score ≥0.2 for non-canonical splice nucleotides) does not apply because SpliceAI max delta is 0.00 and this is an exonic synonymous variant, not a splice region variant. Details ▾Hide ▴
Evidence considered
- HCI prior not found for this variant. SpliceAI max delta = 0.00
- below the PP3 threshold of ≥0.2.
Sources
PP4 No MSI-H tumor data or MMR protein expression data are available for this variant. VCEP MSH6 PP4 requires MSI-H colorectal/endometrial tumors and/or loss of MMR protein expression consistent with the variant location. No such clinical tumor data have been identified. Details ▾Hide ▴
Evidence considered
- No tumor MSI/IHC data available for this variant.
Still missing
- No tumor phenotype data reported.
BA1 The gnomAD v4 grpmax filtering allele frequency for c.2526T>G is 0.0001539 (0.015%), which is far below the VCEP MSH6 BA1 stand-alone threshold of ≥0.0022 (0.22%). The variant does not meet the BA1 frequency criterion. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 0.0001539 (0.015%)
- below BA1 threshold of ≥0.0022 (0.22%).
Sources
BS1 The gnomAD v4 grpmax filtering allele frequency for c.2526T>G is 0.0001539 (0.015%), which falls below the VCEP MSH6 BS1 threshold of ≥0.00022 (0.022%). The variant is too rare in population databases to qualify for BS1. Details ▾Hide ▴
Evidence considered
- gnomAD v4 grpmax FAF = 0.0001539
- below BS1 threshold of ≥0.00022.
Sources
BS2 No evidence of co-occurrence in trans with a known pathogenic MSH6 variant in a patient with colorectal cancer after age 45 has been identified. VCEP BS2 requires confirmed-phase trans co-occurrence with a pathogenic variant in an individual without CMMRD features. Details ▾Hide ▴
Evidence considered
- No trans co-occurrence data available.
Still missing
- No phase-confirmed co-occurrence studies reported.
BS3 No variant-specific functional data demonstrating benign impact are available for c.2526T>G. VCEP MSH6 BS3 requires calibrated functional assays with functional odds for pathogenicity ≤0.05, or synonymous/intronic variants with no mRNA aberration. While the variant is synonymous, no laboratory mRNA assays confirming normal splicing have been performed. Details ▾Hide ▴
Evidence considered
- No functional assay data available for this variant. BS3 requires experimental confirmation.
Still missing
- No mRNA studies with nonsense-mediated decay inhibition have been performed to confirm absence of splicing aberration.
BS4 No segregation data demonstrating lack of co-segregation with disease are available for this variant. VCEP BS4 requires pedigrees with a combined Bayes Likelihood Ratio meeting defined thresholds. Details ▾Hide ▴
Evidence considered
- No co-segregation or lack-of-segregation data available.
Still missing
- No family segregation studies reported.
BP5 No tumor data (MSS tumors, retained MMR protein expression, or BRAF V600E/MLH1 methylation) are available for this variant. VCEP MSH6 BP5 requires observation of MSS tumors without MMR loss or BRAF/MLH1 methylation evidence inconsistent with Lynch syndrome. Details ▾Hide ▴
Evidence considered
- No tumor phenotype data available.
Still missing
- No tumor studies reported for this variant.
Not applicable · 12· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 is not applicable to synonymous variants. The VCEP MSH6 PVS1 rules are limited to nonsense, frameshift, canonical splice site, and initiation codon variants. c.2526T>G (p.Ala842=) is a synonymous substitution with no predicted effect on splicing (SpliceAI max delta = 0.00). Details ▾Hide ▴
Evidence considered
- Synonymous variant with no predicted splicing impact
- does not fall into any PVS1 null-variant bucket per VCEP MSH6 rules.
Sources
PS1 N/APS1 is not applicable to synonymous variants. The VCEP MSH6 PS1 rules require a missense substitution encoding the same amino acid change as a known pathogenic/likely pathogenic variant, or a variant affecting the same non-canonical splice nucleotide as a known pathogenic splice variant. c.2526T>G is synonymous and does not alter the amino acid. Details ▾Hide ▴
Evidence considered
- Synonymous variant does not encode an amino acid change
- PS1 missense and splice comparator rules do not apply.
PS4 VCEPPS4 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
PM1 VCEPPM1 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
PM5 N/APM5 requires a missense change at an amino acid residue where a different pathogenic/likely pathogenic missense variant has been established. c.2526T>G is a synonymous variant (p.Ala842=) and does not alter the amino acid; no missense comparator analysis can be performed. The pm5_candidates artifact confirms ineligibility. Details ▾Hide ▴
Evidence considered
- Synonymous variant
- PM5 not applicable per VCEP same-residue missense rules.
Sources
pm5_candidates
PM6 VCEPPM6 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
PP2 VCEPPP2 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
PP5 VCEPPP5 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
BP1 VCEPBP1 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
BP2 VCEPBP2 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
BP6 VCEPBP6 is explicitly designated as Not Applicable by the ClinGen InSiGHT Hereditary Colorectal Cancer/Polyposis VCEP for MSH6. Details ▾Hide ▴
Evidence considered
- VCEP rules state BP6 is not for use per ClinGen SVI VCEP Review Committee recommendation.
Sources
PS5 N/APS5 is not included in the VCEP MSH6 criteria; PP5 is also explicitly designated as Not Applicable by this VCEP. PS5 is not assessed under this framework. Details ▾Hide ▴
Identifiers
- Gene
- MSH6
- Transcript
- NM_000179.3
- Coding (HGVS c.)
- NM_000179.3:c.2526T>G
- Protein (HGVS p.)
- NP_000170.1:p.(Ala842=)
- GRCh38
- chr2:47800509 T>G
- GRCh37
- chr2:48027648 T>G
- ClinVar
- 2861018, 186376
Gene diagram
Every interpreted variant in MSH6, mapped onto the exon structure of NM_000179.3. Select a row to find it on the plot.
MSH6NM_000179.3
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 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
13 / 1,613,006 alleles
AF 8.06e-06 · 0 homozygotes · FAF 0.000154
gnomAD v2.1
9 / 248,608 alleles
AF 3.62e-05 · 0 homozygotes · FAF 0.000255
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 8.1e-06 · 13 / 1,613,006 alleles · 0 hom · FAF 0.00015
| East Asian12 / 44,896 | 0.00027 |
| European (non-Finnish)1 / 1,179,774 | 8.5e-07 |
0 alternate alleles recorded in 8 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 3.6e-05 · 9 / 248,608 alleles · 0 hom · FAF 0.00026
| East Asian9 / 18,336 | 0.00049 |
0 alternate alleles recorded in 7 other groups: African/African American, Admixed American, Ashkenazi Jewish, European (Finnish), European (non-Finnish), Remaining individuals, South Asian.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 8.05949e-06; MAF= 0.00081%, 13/1613006 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000267284; MAF= 0.02673%, 12/44896 alleles, homozygotes = 0); grpmax FAF= 0.0001539.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.62016e-05; MAF= 0.00362%, 9/248608 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000490838; MAF= 0.04908%, 9/18336 alleles, homozygotes = 0); grpmax FAF= 0.00025523.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- Not available
- BayesDel
- Not available
How the predictions were used
BP4 SupportingSpliceAI predicts no splicing impact for this synonymous variant (max delta score = 0.00, ≤0.1). Per the VCEP MSH6 BP4_Supporting rule, synonymous variants with SpliceAI delta score ≤0.1 meet BP4_Supporting. Details ▾Hide ▴
Evidence considered
- SpliceAI max delta = 0.00
- well below the BP4_Supporting threshold of ≤0.1 for synonymous variants. REVEL and BayesDel are not applicable (synonymous variant). HCI prior not found.
Sources
BP7 Supportingc.2526T>G is a synonymous (silent) variant located at coding position 2526 in exon 4 (c.628-3172), well within the exon interior and far from canonical splice sites. Per VCEP MSH6 BP7, synonymous variants at or beyond the -21/+7 splice region meet BP7_Supporting. Variants may satisfy both BP7 and BP4 per VCEP rules. Details ▾Hide ▴
Evidence considered
- Synonymous variant at c.2526 in exon 4 (spanning c.628-3172)
- far from exon-intron boundaries. SpliceAI confirms no predicted splice impact (delta=0.00).
Sources
PP3 VCEP MSH6 PP3 criteria do not apply to this variant. The HCI prior lookup for c.2526T>G returned no result (variant not in the MSH6 HCI priors table). The SpliceAI-based PP3 rule (delta score ≥0.2 for non-canonical splice nucleotides) does not apply because SpliceAI max delta is 0.00 and this is an exonic synonymous variant, not a splice region variant. Details ▾Hide ▴
Evidence considered
- HCI prior not found for this variant. SpliceAI max delta = 0.00
- below the PP3 threshold of ≥0.2.
Sources
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
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
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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.Describes the ACMG/AMP standards and guidelines for interpretation of sequence variants, including the five-tier classification system and evidence weighting framework. This is a general guideline document that does not mention any specific MSH6 variants.Does not name this variant
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PMID 31672839 ↗Management of patients with increased risk for familial pancreatic cancer: updated recommendations from the International Cancer of the Pancreas Screening (CAPS) Consortium.Updated recommendations from the International Cancer of the Pancreas Screening Consortium for management of individuals at increased risk for familial pancreatic cancer. Mentions Lynch syndrome genes generally but does not discuss any specific MSH6 variants.Does not name this variant
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PMID 15604628 ↗Genetic cancer risk assessment and counseling: recommendations of the national society of genetic counselors.Trepanier A et al. · 2004Provides genetic cancer risk assessment and counseling recommendations from the National Society of Genetic Counselors. Lists MSH6 as one of the DNA mismatch repair genes associated with HNPCC but does not discuss any specific MSH6 variants.Does not name this variant
Quoted passage
DNA mismatch repair genes—MLH1, MSH2, PMS1, PMS2, MSH6, MSH3
Table I (Hereditary Syndromes), MSH6 listed as HNPCC gene
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PMID 23535968 ↗Informing family members of individuals with Lynch syndrome: a guideline for clinical geneticists.Provides a guideline for clinical geneticists on informing family members of individuals with Lynch syndrome. Discusses MMR gene testing and family communication but does not mention any specific MSH6 variants or c.2526T>G.Does not name this variant
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PMID 25356965 ↗ACMG policy statement: updated recommendations regarding analysis and reporting of secondary findings in clinical genome-scale sequencing.ACMG policy statement on updated recommendations for analysis and reporting of secondary findings in clinical genome-scale sequencing. Does not discuss specific MSH6 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.Stoffel EM et al. · 2015ASCO endorsement of ESMO clinical practice guidelines for hereditary colorectal cancer syndromes. Discusses Lynch syndrome management including MSH6 but does not mention c.2526T>G or any specific MSH6 nucleotide variants.Does not name this variant
Quoted passage
for women with MSH6 mutations, the risk for endometrial cancer may surpass the lifetime CRC risk
MSH6 is mentioned in context of Lynch syndrome gene list and endometrial cancer risk
-
PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.Describes Sherloc, a refinement of the ACMG-AMP variant classification criteria. Background review paper that does not discuss specific MSH6 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
13 / 1,613,006 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
5 Likely benign · 1 Likely Benign · 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/1578294885
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/186376/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/2-48027648-T-G?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr2-47800509-T-G?dataset=gnomad_r4
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/2-47800509-T-G
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_000179.3%3Ac.2526…
- OncoKB ↗www.oncokb.org/gene/MSH6/A842=
- COSMIC ↗cancer.sanger.ac.uk/cosmic/search?q=MSH6+c.2526T%3EG
- 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= 8.05949e-06; MAF= 0.00081%, 13/1613006 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000267284; MAF= 0.02673%, 12/44896 alleles, homozygotes = 0); grpmax FAF= 0.0001539.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 3.62016e-05; MAF= 0.00362%, 9/248608 alleles, homozygotes = 0) and has highest observed frequency in the East Asian population (AF= 0.000490838; MAF= 0.04908%, 9/18336 alleles, homozygotes = 0); grpmax FAF= 0.00025523.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Likely benign (5 clinical laboratories) and as Likely Benign (1 clinical laboratory) and as Benign (1 clinical laboratory). (ClinVarID = 186376)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00).
Functional
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
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.