Starting

Initialising…

MSH2

Final classification

VUS

MSH2 c.793-11_794dup · p.?

MSH2

The MSH2 c.793-11_794dup (NP_000242.1:p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.

Gene

MSH2

Transcript

NM_000251.3

HGVS · transcript:coding

NM_000251.3:c.793-11_794dup

Consequence

N/A

GRCh38

chr2:47414256 T>TTCTTAATTTTAGG

GRCh37

chr2:47641395 T>TTCTTAATTTTAGG

Basis Official InSiGHT Hereditary Colorectal Cancer/Polyposis CSPEC final-classification framework (criteria-combination rules derived from Richards et al. 2015 and retrieved in final_classification_framework.json) was applied to the adjudicated criteria. ▾

Official InSiGHT Hereditary Colorectal Cancer/Polyposis CSPEC final-classification framework (criteria-combination rules derived from Richards et al. 2015 and retrieved in final_classification_framework.json) was applied to the adjudicated criteria.

Classification rationale

PM2PP3 VUS

MSH2 c.793-11_794dup

The MSH2 c.793-11_794dup (NP_000242.1:p.?) variant has not been observed in somatic cancers in COSMIC and has not been reported in ClinVar.¹ This variant is absent from gnomAD v2.1 and gnomAD v4.1; in gnomAD v4.1 the observed allele frequency is 0, which is below the MSH2 PM2_Supporting threshold of less than 0.00002.² SpliceAI predicts a splice effect with a maximum delta score of 0.71, which is above the MSH2 PP3 threshold of 0.2 for non-canonical splice variants and above the BP4 no-impact threshold of 0.1.³

PM2 + PP3 → VUS

1 evidence.json.results.cosmicevidence.json.results.clinvar

2 evidence.json.results.gnomad.GNOMAD_V2_1evidence.json.results.gnomad.GNOMAD_V4_1MSH2/criteria.json:PM2

3 evidence.json.results.spliceaiMSH2/criteria.json:PP3MSH2/criteria.json:BP4

Gene diagram · NM_000251.3 · variants mapped to exon structure

MSH2 NM_000251.3

Fetching transcript structure from UCSC…

Applied criteria · 2 met · select any tile

Met

Not met

Not assessed

N/A

Strength very strong supporting

Pathogenic evidence

PVS

Benign evidence

—

Rationale

Select a criterion.

Sources

Evidence used

Gaps remaining

Rule

—

Research & evidence

Population frequency

gnomAD v4.1

gnomAD v2.1

v4.1

Absent from gnomAD v4.1.

v2.1

Absent from gnomAD v2.1.

Allele frequency by ancestry

three datasets · side by side

gnomAD v4.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v2.1

Absent · 0 / ?
0 hom

Not observed in any ancestry group.

gnomAD v4 ↗ gnomAD v2 ↗

ClinVar

This variant is absent from ClinVar.

ClinVar ↗

In silico

SpliceAI predicts possible splice impact for this variant (max delta score = 0.71).

SpliceAI ↗

Functional No data

No calibrated functional assay or RNA evidence was identified for this variant.

OncoKB ↗

COSMIC

Somatic evidence

COSMIC

This variant has not previously been reported in somatic cancers (COSMIC).

Hotspots

This variant does not lie in a statistically significant cancer hotspot.

COSMIC ↗

Sources & reference links

7Sources

CSpec VCEP

ClinVar

gnomAD v2.1

gnomAD v4.1

SpliceAI

OncoKB

COSMIC