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LYFE SCIENCES
Project: HERA
NM_001330437.1:c.526-8C>A
p.?  ·  PTPN11
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Classification rationale
1

The PTPN11 NM_001330437.1:c.526-8C>A (NP_001317366.1:p.?) variant has been reported in ClinVar and is classified as Benign by the ClinGen RASopathy Variant Curation Expert Panel.

clinvar ↗
2

This variant is present in gnomAD v2.1 at 0.06730% and in gnomAD v4.1 at 0.13022%, which are both above the PTPN11 BA1 threshold of 0.05% and the BS1 threshold of 0.025%.

gnomad_v2 ↗ gnomad_v4 ↗ cspec ↗
3

SpliceAI predicts no significant splice impact, with a maximum delta score of 0.06, which supports BP4 and does not support PP3 for a splice-region effect.

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= 0.000673019; MAF= 0.06730%, 190/282310 alleles, homozygotes = 1) and has highest observed frequency in the European (non-Finnish) population (AF= 0.00129804; MAF= 0.12980%, 167/128656 alleles, homozygotes = 0); grpmax FAF= 0.00111834.
gnomAD v4.1This variant is present in gnomAD v4.1 (AF= 0.00130217; MAF= 0.13022%, 2078/1595796 alleles, homozygotes = 4) and has highest observed frequency in the European (non-Finnish) population (AF= 0.001701; MAF= 0.17010%, 1980/1164018 alleles, homozygotes = 2); grpmax FAF= 0.00163779.
gnomAD v2 ↗ gnomAD v4 ↗
ClinVar evidence
02
ClinVar
This variant has been reported in ClinVar as Benign (12 clinical laboratories) and as Likely benign (9 clinical laboratories) and as Uncertain significance (1 clinical laboratory) and as Benign by ClinGen RASopathy Variant Curation Expert Panel (expert panel). (ClinVarID = 36709)
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 = 0.06).
SpliceAI ↗
COSMIC evidence
05
COSMIC
This variant has previously been reported in somatic cancers (COSMIC; COSV105261528, n = 1 times).
COSMIC ↗
06
Cancer hotspots
No cancer hotspot summary recorded.