Back
LYFE SCIENCES
Project: HERA
NM_000179.3:c.2091T>C
p.Asp697=  ·  MSH6
Starting
Initialising…
0%
Legacy Engine
Ready
View Legacy →
Classification rationale
1

The MSH6 c.2091T>C (p.Asp697=) variant has not been observed in somatic cancers in COSMIC.

2

This variant is absent from gnomAD v2.1 and gnomAD v4.1, and its gnomAD v4.1 frequency is therefore below the MSH6 PM2_Supporting threshold of less than 0.00002.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

This synonymous exon 4 variant is far from the splice junction boundaries used for MSH6 BP7, and SpliceAI predicts no meaningful splice effect with a maximum delta score of 0.02, supporting BP7 and BP4 while arguing against PP3 or PVS1 based on the currently available evidence.

spliceai ↗ cspec ↗
Applied criteria
Met
Not met
Not assessed
N/A
Very strong
Strong
Moderate
Supporting
Pathogenic evidence
PVS
PVS1
PS
PS1
PS2
PS3
PS4
PM
PM1
PM2
PM3
PM4
PM5
PM6
PP
PP1
PP2
PP3
PP4
PP5
Benign evidence
BA
BA1
BS
BS1
BS2
BS3
BS4
BP
BP1
BP2
BP3
BP4
BP5
BP6
BP7
PVS1
—
—
Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
—
Research and evidence
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (1 clinical laboratory) and as Benign (1 clinical laboratory).
ClinVar ↗
Functional evidence
03
Functional
OncoKB: Unknown Oncogenic Effect
OncoKB identified curated literature and non-variant-specific oncogenicity context for review; listed oncogenicity label: Unknown Oncogenic Effect.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.02).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
Cancer hotspots evidence
06
Cancer hotspots Not found
This variant does not lie in a statistically significant hotspot.
ResidueD697
Hotspots ↗