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LYFE SCIENCES
Project: HERA
NM_000535.7:c.23+32dup
p.?  ·  PMS2
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Classification rationale
1

The PMS2 NM_000535.7:c.23+32dup (NP_000526.2:p.?) variant has been reported in ClinVar as likely benign by one clinical laboratory.

clinvar ↗
2

In gnomAD, this variant has a v4.1 total allele frequency of 5.0248e-05 (81/1612004 alleles) and a grpmax filtering allele frequency of 5.301e-05, which is above the PMS2 PM2 threshold of 0.00002 but below the BS1 threshold of 0.00028.

gnomad_v4 ↗ cspec ↗
3

This intronic duplication is located at c.23+32, beyond the PMS2 BP7 boundary of +7, and SpliceAI predicts no significant splice impact with a maximum delta score of 0.02, supporting BP7 and BP4 while arguing against PP3 and PVS1.

cspec ↗ spliceai ↗
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= 7.99226e-06; MAF= 0.00080%, 2/250242 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.77292e-05; MAF= 0.00177%, 2/112808 alleles, homozygotes = 0); grpmax FAF= 2.94e-06.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 5.0248e-05; MAF= 0.00502%, 81/1612004 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 6.52867e-05; MAF= 0.00653%, 77/1179414 alleles, homozygotes = 0); grpmax FAF= 5.301e-05.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Likely benign (1 clinical laboratory).
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 = 0.02).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV56151367, n = 1 times).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.