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LYFE SCIENCES
Project: HERA
NM_000179.3:c.4002-28_4002-26dup
p.?  ·  MSH6
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Classification rationale
1

The MSH6 c.4002-28_4002-26dup (p.?) variant has been reported in ClinVar with benign and likely benign interpretations, and no expert panel assertion was identified.

clinvar ↗
2

This variant is common in population databases, including gnomAD v4.1 with an overall allele frequency of 0.00134155 and an East Asian allele frequency of 0.0283305 (1159/40910 alleles; 5 homozygotes), which is above the MSH6 BA1 threshold of 0.0022; similarly high frequencies are present in gnomAD v2.1 and gnomAD-Canada.

gnomad_v4 ↗ gnomad_v2 ↗ gnomad_canada ↗ cspec ↗
3

For this intronic duplication, SpliceAI predicts no significant splice impact with a maximum delta score of 0.05, which is below the MSH6 BP4 no-impact threshold of 0.1 and below the PP3 splice-defect threshold of 0.2.

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
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Rationale
Select a criterion to inspect its explanation.
Evidence used
  • —
Gaps remaining
  • —
Rule
—
Publications
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Research and evidence
gnomAD v2.1 evidence
v2.1
gnomAD v4.1 evidence
v4.1
01
Population
gnomAD v2.1This variant is present in gnomAD v2.1 (AF= 0.00252012; MAF= 0.25201%, 570/226180 alleles, homozygotes = 2) and has highest observed frequency in the East Asian population (AF= 0.0313601; MAF= 3.13601%, 445/14190 alleles, homozygotes = 2); grpmax FAF= 0.0565538.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.00134155; MAF= 0.13415%, 1883/1403604 alleles, homozygotes = 6) and has highest observed frequency in the East Asian population (AF= 0.0283305; MAF= 2.83305%, 1159/40910 alleles, homozygotes = 5); grpmax FAF= 0.0269749.
gnomAD CanadaThis variant is present in gnomAD-Canada v1.0 (AF= 0.00418751; MAF= 0.41875%, 77/18388 alleles, homozygotes = 3) and has highest observed frequency in the eas population (AF= 0.0470852; grpmax FAF95= 0.0377698).
gnomAD v2 ↗ gnomAD v4 ↗ gnomAD 🇨🇦 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (2 clinical laboratories) and as Likely benign (1 clinical laboratory). (ClinVarID = 926536)
ClinVar ↗
03
Functional
No functional summary recorded.
OncoKB ↗
In silico evidence
04
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has not previously been reported in somatic cancers (COSMIC).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.