Classification rationale
In progress — classification not generated yet.
No rationale recorded.
PTPN11
Final classification
In progress — classification not generated yet.
PTPN11 c.1505C>T · p.Ser502Leu
PTPN11
In progress — classification not generated yet.
In progress — classification not generated yet.
Gene diagram
· NM_002834.4 · variants mapped to exon structure
PTPN11
NM_002834.4
Fetching transcript structure from UCSC…
Applied criteria · 0 applied · 28 assessed
Applied · 0
No criteria were applied for this variant.
Assessed · not applied
Pathogenic
PVS1
PS1
PS2
PS3
PS4
PM1
PM2
PM3
PM4
PM5
PM6
PP1
PP2
PP3
PP4
PP5
Benign
BA1
BS1
BS2
BS3
BS4
BP1
BP2
BP3
BP4
BP5
BP6
BP7
Research & evidence
Population frequency
gnomAD v4.1
gnomAD v2.1
v4.1
This variant is present in gnomAD v4.1 (AF= 0; MAF= 0.00000%, 0/1614128 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/75032 alleles, homozygotes = 0).
v2.1
Absent from gnomAD v2.1.
🇨🇦 CA
Absent from gnomAD-Canada v1.0.
Allele frequency by ancestry
three datasets · side by side
gnomAD v4.1
Absent
· 0 / 1,614,128
0 hom
0 hom
Not observed in any ancestry group.
+ 10 not observed (Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American, European (non-Finnish))
gnomAD v2.1
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
gnomAD Canada 🇨🇦
Absent
· 0 / ?
0 hom
0 hom
Not observed in any ancestry group.
COSMIC
Cancer hotspots
Somatic evidence
Hotspot
COSMIC
In progress — evidence not uploaded yet.
Hotspots
This variant lies in a statistically significant hotspot.
Sources & reference links
9Sources
Triaged references · 8 PMIDs not cited in assessment
15834506 ↗
Functional analysis of PTPN11/SHP-2 mutants identified in Noonan syndrome and childhood leukemia.
ONCOKB
12325025 ↗
PTPN11 mutations in Noonan syndrome type I: detection of recurrent mutations in exons 3 and 13.
CLINVAR
15710330 ↗
Prognostic, therapeutic, and mechanistic implications of a mouse model of leukemia evoked by Shp2 (PTPN11) mutations.
CLINVAR
15928039 ↗
The mutational spectrum of PTPN11 in juvenile myelomonocytic leukemia and Noonan syndrome/myeloproliferative disease.
CLINVAR
16358218 ↗
Diversity and functional consequences of germline and somatic PTPN11 mutations in human disease.
CLINVAR
17020470 ↗
PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype.
CLINVAR
17910045 ↗
Mutations of FLT3, NRAS, KRAS, and PTPN11 are frequent and possibly mutually exclusive in high hyperdiploid childhood acute lymphoblastic leukemia.
CLINVAR
21533187 ↗
Loss-of-function mutations in PTPN11 cause metachondromatosis, but not Ollier disease or Maffucci syndrome.
CLINVAR