About PTPN11
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
PTPN11 c.179G>T, p.(Gly60Val)
Classification
Likely pathogenic
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.
Likely pathogenic.A likely pathogenic classification under the recorded framework.
In plain language
Gene-level background from the recorded interpretation.
Words with a dotted underline have a short definition. Hover or tap them.
LYFE Sciences is an AI system, and it can make mistakes.
Criteria may be applied incorrectly, sources may be misread, and a
confident-looking classification can still be wrong.
Double-check every criterion and its underlying evidence
before relying on any call.
01The reasoning
How it was classified
The recorded framework is ClinGen PTPN11 VCEP v1.0. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.
Recorded applied criteria
The applied criteria and their strengths are shown as assessed under the stated framework.
Pathogenic evidence criteria: 6
Benign evidence criteria: 0
Pathogenic criteria applied · 6
PS3Supporting
PS3 · supporting
SHP2 G60V demonstrated increased basal phosphatase activity compared to wild-type SHP2 in a quantitative DiFMUP-based phosphatase assay (PMID:30375388). This assay type (SHP-2 Phosphatase Activity) is an approved functional assay for PTPN11 per the RASopathy VCEP supplemental material. The VCEP spreadsheet assigns PS3_Supporting strength for approved functional studies. G60V showed intermediate activation between F285S and S502P/E76K and conferred resistance to allosteric inhibition by SHP099 in cellular assays, consistent with a gain-of-function mechanism.
PM1Moderate
PM1 · moderate
Gly60 is located in the N-SH2 domain of SHP2, a critical functional domain that forms the autoinhibitory interface with the PTP domain. Multiple pathogenic missense changes have been reported at this residue (G60A, G60C, G60V), and disruption of Gly60 destabilizes the autoinhibited conformation, leading to constitutive phosphatase activation. The N-SH2 domain is a well-established critical functional domain in SHP2.
PM2Moderate
PM2 · moderate
NM_002834.4:c.179G>T is completely absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), meeting the VCEP requirement of complete absence from all population databases.
PM5Moderate
PM5 · moderate
A different missense change at the same residue, Gly60Ala (c.179G>C, p.Gly60Ala), has been previously reported as a pathogenic variant in Noonan syndrome (PMID:11992261). Both G60A and G60V are non-conservative substitutions at a glycine residue critical to the autoinhibitory interface. Under the RASopathy VCEP, one established pathogenic missense at the same residue qualifies for PM5 at moderate strength.
PP2Supporting
PP2 · supporting
The RASopathy VCEP explicitly states that PP2 is applicable to all RASopathy genes described and curated in the specification. PTPN11 is a RASopathy gene, and c.179G>T is a missense variant in a gene where missense variants are a common mechanism of disease.
PP3Supporting
PP3 · supporting
Multiple lines of computational evidence support a deleterious effect: REVEL score of 0.931 (strongly deleterious) and BayesDel score of 0.596 (deleterious). Both in silico predictors independently suggest a damaging effect on the gene product. SpliceAI predicts no significant splice impact (max delta score 0.05), indicating the effect is at the protein level.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Likely pathogenic
ClinGen RASopathy Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.0 v1.0 lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PS3 supporting, PM1 moderate, PM2 moderate, PM5 moderate, PP2 supporting, PP3 supporting; combination = 3 moderate + 3 supporting, which maps to Likely Pathogenic.
02The sources
Evidence at a glance
Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.
gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded
gnomAD v4.1 allele counts were not recorded for this variant.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.050 maximum delta
Recorded SpliceAI maximum delta score: 0.050. Refer to the recorded PP3/BP4 rationale for interpretation.
ClinVar submissions
11 reported laboratory submissions
9 Pathogenic · 2 Likely pathogenic. ClinVar API review status: criteria provided, multiple submitters, no conflicts.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PTPN11, a protein tyrosine phosphatase, is altered in various solid and hematologic malignancies.
COSMIC
Cancer Hotspots
Somatic evidence
64 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV61005028, n = 64 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under ClinGen PTPN11 VCEP v1.0, with the data and sources behind each one.
29 criteria with recorded statuses: 6 met · 13 not met · 0 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_002834.4:c.179G>T (p.Gly60Val) in PTPN11 is a missense variant in the N-SH2 domain, a critical functional domain that regulates SHP2 autoinhibition.
This variant is completely absent from gnomAD v2.1, v4.1, and gnomAD-Canada population databases (PM2).
Functional studies demonstrate that SHP2 G60V exhibits increased basal phosphatase activity compared to wild-type, consistent with a gain-of-function mechanism in RASopathies (PS3_Supporting).
The variant is located at a residue (Gly60) within the N-SH2 domain where multiple pathogenic missense changes have been reported (PM1).
A different pathogenic missense change at the same residue, Gly60Ala (c.179G>C), has been reported in Noonan syndrome (PM5).
Multiple in silico predictors support a deleterious effect: REVEL score 0.931 and BayesDel score 0.596 (PP3).
PP2 is applicable per the RASopathy VCEP specification for all curated RASopathy genes (PP2).
This variant has been reported in ClinVar as Pathogenic by 9 clinical laboratories and Likely pathogenic by 2 clinical laboratories (ClinVar variation ID 55797).
No criteria match.
Met · 6
PS3 SupportingSHP2 G60V demonstrated increased basal phosphatase activity compared to wild-type SHP2 in a quantitative DiFMUP-based phosphatase assay (PMID:30375388). This assay type (SHP-2 Phosphatase Activity) is an approved functional assay for PTPN11 per the RASopathy VCEP supplemental material. The VCEP spreadsheet assigns PS3_Supporting strength for approved functional studies. G60V showed intermediate activation between F285S and S502P/E76K and conferred resistance to allosteric inhibition by SHP099 in cellular assays, consistent with a gain-of-function mechanism. Details ▾Hide ▴
Evidence considered
- SHP2 G60V exhibits increased basal phosphatase activity relative to WT (DiFMUP assay
- Fig. 3b
- PMID:30375388)
- SHP2 G60V-expressing cells show ~5-fold elevated pErk levels (Fig. 6b
- VCEP-approved SHP-2 Phosphatase Activity assay type
- proposed strength PS3_Supporting
Still missing
- Study not yet in VCEP-approved reference list
- may need formal VCEP submission for approval
Sources
PM1 ModerateGly60 is located in the N-SH2 domain of SHP2, a critical functional domain that forms the autoinhibitory interface with the PTP domain. Multiple pathogenic missense changes have been reported at this residue (G60A, G60C, G60V), and disruption of Gly60 destabilizes the autoinhibited conformation, leading to constitutive phosphatase activation. The N-SH2 domain is a well-established critical functional domain in SHP2. Details ▾Hide ▴
Evidence considered
- Gly60 resides in the N-SH2 domain
- part of the autoinhibitory interface with PTP domain (PMID:11992261)
- Multiple pathogenic missense variants at Gly60 (G60A
- G60C
- G60V) reported in Noonan syndrome and cancer
Still missing
- Residue not explicitly listed in VCEP-approved PM1 residue list
- domain-level application
Sources
PM2 ModerateNM_002834.4:c.179G>T is completely absent from gnomAD v2.1 (exomes), gnomAD v4.1 (exomes), and gnomAD-Canada v1.0 (genomes), meeting the VCEP requirement of complete absence from all population databases. Details ▾Hide ▴
Evidence considered
- Absent from gnomAD v2.1
- Absent from gnomAD v4.1
- Absent from gnomAD-Canada v1.0
Sources
PM5 ModerateA different missense change at the same residue, Gly60Ala (c.179G>C, p.Gly60Ala), has been previously reported as a pathogenic variant in Noonan syndrome (PMID:11992261). Both G60A and G60V are non-conservative substitutions at a glycine residue critical to the autoinhibitory interface. Under the RASopathy VCEP, one established pathogenic missense at the same residue qualifies for PM5 at moderate strength. Details ▾Hide ▴
Evidence considered
- G60A (c.179G>C) reported as pathogenic Noonan syndrome variant in Tartaglia et al. 2002 (Table 3)
Sources
PP2 SupportingThe RASopathy VCEP explicitly states that PP2 is applicable to all RASopathy genes described and curated in the specification. PTPN11 is a RASopathy gene, and c.179G>T is a missense variant in a gene where missense variants are a common mechanism of disease. Details ▾Hide ▴
PP3 SupportingMultiple lines of computational evidence support a deleterious effect: REVEL score of 0.931 (strongly deleterious) and BayesDel score of 0.596 (deleterious). Both in silico predictors independently suggest a damaging effect on the gene product. SpliceAI predicts no significant splice impact (max delta score 0.05), indicating the effect is at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL score 0.931 (deleterious)
- BayesDel score 0.596 (deleterious)
Sources
Not met · 13 · evaluated, threshold not reached
PS1 PS1 requires the same amino acid change (Gly60Val) to have been previously established as pathogenic via a different nucleotide change. No evidence was found that G60V has been established as pathogenic through an alternate nucleotide substitution. Details ▾Hide ▴
Evidence considered
- No alternate nucleotide change producing p.Gly60Val identified as pathogenic
PS2 No de novo occurrence with confirmed paternity and maternity was identified for NM_002834.4:c.179G>T in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No de novo data identified in reviewed literature
Still missing
- De novo testing data not available in reviewed literature
PS4 While ClinVar contains 11 clinical laboratory submissions classifying this variant as Pathogenic (9) or Likely pathogenic (2), these represent submissions, not independently ascertained proband occurrences. No literature was identified reporting ≥1 independent occurrence of NM_002834.4:c.179G>T in a RASopathy patient. Notably, PMID:11992261 reported G60A (c.179G>C) but not G60V. Details ▾Hide ▴
Evidence considered
- ClinVar variation ID 55797: 11 submissions
- 0 expert panel classifications
Still missing
- No independent proband counts available for this specific variant
Sources
PM6 No assumed or confirmed de novo occurrence of NM_002834.4:c.179G>T was identified in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No de novo data identified
Still missing
- De novo data not available
PP1 No co-segregation data with informative meioses is available for this variant in the reviewed literature. Details ▾Hide ▴
Evidence considered
- No segregation data identified
Still missing
- Segregation data not available
BA1 The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. Allele frequency is 0%, well below the VCEP BA1 threshold of ≥0.05%. Details ▾Hide ▴
Evidence considered
- Absent from all population databases
- AF = 0%
Sources
BS1 The variant is absent from gnomAD v2.1, v4.1, and gnomAD-Canada. Allele frequency is 0%, well below the VCEP BS1 threshold of ≥0.025%. Details ▾Hide ▴
Evidence considered
- Absent from all population databases
- AF = 0%
Sources
BS2 The VCEP specifies that general population data should not be used for BS2 in RASopathies due to variable expressivity. No well-phenotyped healthy family members (≥3 instances) have been identified with this variant. Details ▾Hide ▴
Evidence considered
- No well-phenotyped healthy individuals identified with this variant
Still missing
- No phenotype data for healthy carriers available
Sources
BS3 Functional data from PMID:30375388 demonstrates that SHP2 G60V has increased basal phosphatase activity compared to wild-type, consistent with a gain-of-function mechanism. No functional studies suggest a benign or no-effect outcome for this variant. Details ▾Hide ▴
Evidence considered
- G60V shows activating effect in phosphatase assay
- no evidence of benign functional impact
Sources
BS4 No segregation data demonstrating lack of segregation in affected family members is available for this variant. Details ▾Hide ▴
Evidence considered
- No segregation data available
Still missing
- Segregation data not available
BP2 No data available on whether this variant has been observed in trans with a pathogenic variant or in cis with a pathogenic variant in any inheritance pattern. Details ▾Hide ▴
Evidence considered
- No cis/trans phase data available
Still missing
- Phase data not available
BP4 Multiple lines of computational evidence (REVEL 0.931, BayesDel 0.596) support a deleterious effect on the gene product rather than no impact. BP4 requires evidence suggesting no impact. Details ▾Hide ▴
Evidence considered
- REVEL score 0.931 predicts deleterious effect
- not benign
- BayesDel score 0.596 predicts deleterious effect
Sources
revelbayesdel
BP5 No evidence was identified that this variant has been found in a case with an alternate molecular basis for disease. Details ▾Hide ▴
Evidence considered
- No alternate molecular basis identified
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPPVS1 is not applicable to the RASopathies per the ClinGen RASopathy VCEP v1.0. Loss of function has not been established as a disease mechanism for PTPN11 relative to the RASopathy spectrum. Additionally, c.179G>T (p.Gly60Val) is a missense variant, not a null variant. Details ▾Hide ▴
PM3 VCEPPM3 is not applicable to the RASopathies per the ClinGen RASopathy VCEP v1.0. RASopathies are autosomal dominant disorders. Details ▾Hide ▴
PM4 N/AProtein length changes due to in-frame deletions/insertions or stop-loss variants are not applicable. This is a missense substitution. Details ▾Hide ▴
Evidence considered
- Missense substitution
- not a protein-length change
PP4 VCEPPP4 is not applicable to the RASopathies per the ClinGen RASopathy VCEP v1.0. The VCEP directs use of PS4 for proband counting instead. Details ▾Hide ▴
PP5 VCEPPP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee for the RASopathy VCEP. Details ▾Hide ▴
BP1 N/ABP1 applies only to truncating variants in genes without established LOF correlation to disease per the RASopathy VCEP. This is a missense variant (p.Gly60Val). Details ▾Hide ▴
Evidence considered
- Missense variant
- BP1 is for truncating variants only per VCEP specification
Sources
BP3 N/ANot an in-frame deletion/insertion in a repetitive region. Details ▾Hide ▴
Evidence considered
- Not an in-frame indel
BP6 VCEPBP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee for the RASopathy VCEP. Details ▾Hide ▴
BP7 N/ABP7 applies only to synonymous (silent) variants or intronic/non-coding variants. NM_002834.4:c.179G>T is a missense variant (p.Gly60Val). Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for synonymous/intronic variants
PS5 N/APS5 is not a standard ACMG/AMP criterion and is not included in the RASopathy VCEP criteria. Details ▾Hide ▴
Evidence considered
- Not a recognized ACMG/AMP or VCEP criterion
Identifiers
- Gene
- PTPN11
- Transcript
- NM_002834.4
- Coding (HGVS c.)
- NM_002834.4:c.179G>T
- Protein (HGVS p.)
- NP_002825.3:p.(Gly60Val)
- GRCh38
- chr12:112450359 G>T
- GRCh37
- chr12:112888163 G>T
- ClinVar
- 55797
- COSMIC
- COSV61005028
Gene diagram
Every interpreted variant in PTPN11, mapped onto the exon structure of NM_002834.4. Select a row to find it on the plot.
PTPN11NM_002834.4
Fetching transcript structure from UCSC…
Exons
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Transcript span
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Strand
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Variants mapped
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Source
UCSC ncbiRefSeqCurated
All variants in PTPN11
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Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
Allele count data not recorded
gnomAD v2.1
Allele count data not recorded
gnomAD-Canada v1.0
Allele count data not recorded
Statements
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.931
- BayesDel
- 0.596
How the predictions were used
PP3 SupportingMultiple lines of computational evidence support a deleterious effect: REVEL score of 0.931 (strongly deleterious) and BayesDel score of 0.596 (deleterious). Both in silico predictors independently suggest a damaging effect on the gene product. SpliceAI predicts no significant splice impact (max delta score 0.05), indicating the effect is at the protein level. Details ▾Hide ▴
Evidence considered
- REVEL score 0.931 (deleterious)
- BayesDel score 0.596 (deleterious)
Sources
BP4 Multiple lines of computational evidence (REVEL 0.931, BayesDel 0.596) support a deleterious effect on the gene product rather than no impact. BP4 requires evidence suggesting no impact. Details ▾Hide ▴
Evidence considered
- REVEL score 0.931 predicts deleterious effect
- not benign
- BayesDel score 0.596 predicts deleterious effect
Sources
revelbayesdel
BP7 N/ABP7 applies only to synonymous (silent) variants or intronic/non-coding variants. NM_002834.4:c.179G>T is a missense variant (p.Gly60Val). Details ▾Hide ▴
Evidence considered
- Missense variant
- BP7 is for synonymous/intronic variants
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.931. BayesDel score = 0.596115.
10 paper records listed. 3 cited in the classification.
Cited in the classification
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PMID 11992261 ↗PTPN11 mutations in Noonan syndrome: molecular spectrum, genotype-phenotype correlation, and phenotypic heterogeneity.Tartaglia M et al. · 2002 JunScreened 119 unrelated individuals with Noonan syndrome for PTPN11 mutations. Identified Gly60Ala (c.179G>C) as a pathogenic mutation in 2 cases. The variant c.179G>T (p.Gly60Val) was not reported. The paper established that Gly60 is part of the N-SH2/PTP autoinhibitory interface, with missense changes at this residue causing gain-of-function.→ PM1 → PM5 Does not name this variant
Source detail
179GrC — 2 — Gly60Ala — N-SH2
Location Table 3; Discussion
-
PMID 16263833 ↗Noonan syndrome: relationships between genotype, growth, and growth factors.Limal JM et al. · 2006 JanStudied genotype-growth factor relationships in Noonan syndrome patients with and without PTPN11 mutations. Gly60 is discussed as a residue that hydrogen-bonds with Cys459 of the PTP domain to stabilize the autoinhibited conformation. Gly60Cys (c.178G>T) was mentioned but not Gly60Val (c.179G>T).→ PM1 Does not name this variant
Source detail
Gly60 and Asp61 hydrogen-bond Cys459 of the PTP catalytic cleft, stabilizing the closed inactive conformation of the phosphatase
Location Discussion
-
PMID 30375388 ↗Structural reorganization of SHP2 by oncogenic mutations and implications for oncoprotein resistance to allosteric inhibition.SHP2 G60V was directly tested in phosphatase activity assays using the fluorogenic substrate DiFMUP. G60V showed increased basal phosphatase activity intermediate between F285S and S502P/E76K. In PTPN11-null U2OS cells expressing SHP2 G60V, pErk levels were approximately 5-fold higher than parental cells, and the variant conferred resistance to allosteric inhibition by SHP099.→ PS3 → PM1 Names this variant
Source detail
the basal activity of the SHP2 variants investigated here increases from SHP2 WT < SHP2 F285S < SHP2 G60V < SHP2 S502P < SHP2 E76K
Location Results, SHP2 oncoprotein sensitivity to allosteric modulators; Fig. 3b; Fig. 6b; Methods, Quantification of basal SHP2 phosphatase activity
Context In vitro phosphatase assay using purified recombinant SHP2 proteins with DiFMUP substrate; cellular pErk assay in PTPN11-null U2OS cells expressing SHP2 G60V
Other recorded publications
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PMID 17020470 ↗PTPN11 gene analysis in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype.Bertola DR et al. · 2006Analyzed PTPN11 mutations in 74 Brazilian patients with Noonan syndrome or Noonan-like phenotype. G60A was mentioned in the discussion of mutation spectrum. G60V (c.179G>T) was not identified in this cohort.Does not name this variant
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PMID 18701506 ↗Mutation of genes affecting the RAS pathway is common in childhood acute lymphoblastic leukemia.No paper-specific finding is recorded.
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PMID 22097954 ↗De novo P102L mutation in a patient with Gerstmann-Sträussler-Scheinker disease.Kojović M et al. · 2011Reports a de novo P102L mutation in the PRNP gene in a patient with Gerstmann-Sträussler-Scheinker disease. This paper concerns the prion protein gene and has no relevance to PTPN11 or RASopathies. This paper was incorrectly triaged under the PTPN11 search.Does not name this variant
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PMID 25741868 ↗Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.ACMG/AMP standards and guidelines for the interpretation of sequence variants. This is a methodological reference providing the generic classification framework, not a variant-specific study.Does not name this variant
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PMID 27959697 ↗Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation.Posey JE et al. · 2017Retrospective analysis of 7,374 consecutive patients undergoing whole-exome sequencing to identify multilocus genomic variation. PTPN11 variants were noted in the context of multilocus diagnoses, but NM_002834.4:c.179G>T was not specifically reported.Does not name this variant
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PMID 25173338 ↗2014 ESC Guidelines on diagnosis and management of hypertrophic cardiomyopathy: the Task Force for the Diagnosis and Management of Hypertrophic Cardiomyopathy of the European Society of Cardiology (ESC).No paper-specific finding is recorded.
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PMID 28492532 ↗Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.No paper-specific finding is recorded.
Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.
gnomAD v4.1
Captured gnomAD v4.1 source record
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.050
Open source ↗
ClinVar
9 Pathogenic · 2 Likely pathogenic
Open source ↗
COSMIC
Captured COSMIC source record
Open source ↗
Cancer hotspots
Captured Cancer Hotspots source record
Open source ↗
OncoKB
Captured OncoKB source record
Open source ↗
ClinGen CSpec
Captured ClinGen CSpec source record
Open source ↗
All source links
- ClinGen CSpec ↗cspec.genome.network/cspec/ui/svi/doc/135637576
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/55797/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/12-112888163-G-T?dataset=gnom…
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr12-112450359-G-T?dataset=g…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/12-112450359-G-T
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_002834.4%3Ac.179G…
- OncoKB ↗www.oncokb.org/gene/PTPN11/G60V
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=219049217
- Cancer hotspots ↗www.cancerhotspots.org/
Statements for reports
The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.
gnomAD v4.1
Absent from gnomAD v4.1.
gnomAD v2.1
Absent from gnomAD v2.1.
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Pathogenic (9 clinical laboratories) and as Likely pathogenic (2 clinical laboratories). (ClinVarID = 55797)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.05). REVEL score = 0.931. BayesDel score = 0.596115.
Functional
OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PTPN11, a protein tyrosine phosphatase, is altered in various solid and hematologic malignancies.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV61005028, n = 64 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.