About STAT3
No gene-level summary was recorded for this case.
Previous versions
Variant interpretation report
STAT3 c.1940A>T, p.(Asn647Ile)
Classification
Uncertain significance
Variant description:
No variant summary was recorded for this case.
Five-step scale from benign to pathogenic. This variant is uncertain. Select a step to read what it means.
Uncertain.The recorded classification is uncertain significance.
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 Not recorded. 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: 2
Benign evidence criteria: 0
Pathogenic criteria applied · 2
PM1Moderate
PM1 · moderate
c.1940A>T (p.Asn647Ile) is located in the STAT3 Src homology 2 (SH2) domain (UniProt residues 583–688). The SH2 domain is a well-established mutational hotspot where numerous pathogenic missense variants have been documented in both germline hyper-IgE syndrome and somatic lymphoproliferative disorders. Multiple publications describe clustering of disease-associated missense mutations in the STAT3 SH2 domain.
PM2Supporting
PM2 · supporting
NM_139276.2:c.1940A>T is absent from gnomAD v2.1 (0/251,490 alleles) and extremely rare in gnomAD v4.1 (2/1,614,212 alleles; AF=1.24×10⁻⁶; grpmax FAF=2.8×10⁻⁷). Both are well below the 0.1% PM2 threshold. The variant is also absent from gnomAD-Canada.
Benign criteria applied · 0
No benign criterion marked as applied in the recorded assessment.
Recorded classification: Uncertain significance
gene-specific framework lacked a usable explicit final combination framework, so generic ACMG/AMP 2015 final-combination rules were applied as fallback; applied criteria: PM1 moderate, PM2 supporting; combination = 1 moderate + 1 supporting, which maps to VUS.
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
2 / 1,614,212 alleles
gnomAD v4.1: 2 / 1,614,212 alleles. Recorded AF 1.23899e-06. Recorded homozygote count 0.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0; MAF= 0.00000%, 0/251490 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/16256 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI score
0.000 maximum delta
Recorded SpliceAI maximum delta score: 0.000. Refer to the recorded PP3/BP4 rationale for interpretation.
No listed criterion applied
SpliceAI ↗
ClinVar submissions
3 reported laboratory submissions
2 Uncertain significance · 1 Pathogenic.
Context only
ClinVar ↗
Functional evidence
Statement recorded
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
No listed criterion applied
OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
28 recorded samples
This variant has previously been reported in somatic cancers (COSMIC; COSV52882818, n = 28 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.
Context only
For specialists
Technical detail
ACMG/AMP criteria under Not recorded, with the data and sources behind each one.
26 criteria with recorded statuses: 2 met · 15 not met · 5 not assessed · 4 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.
Met
Not met
Not assessed
Not applicable
NM_139276.2:c.1940A>T (p.Asn647Ile) in STAT3 was assessed using generic ACMG/AMP 2015 criteria (PMID:25741868). No CSPEC/VCEP framework is available for STAT3.
This missense variant is located in the SH2 domain (residues 583–688), a well-established mutational hotspot where numerous pathogenic variants have been identified in both germline hyper-IgE syndrome and somatic lymphoproliferative disorders, satisfying PM1 at moderate strength.
The variant is absent from gnomAD v2.1 (0/251,490 alleles) and extremely rare in gnomAD v4.1 (2/1,614,212 alleles; AF=1.24×10⁻⁶), satisfying PM2 at supporting strength.
In silico predictors do not reach consensus for pathogenicity (REVEL 0.359; BayesDel −0.126; SpliceAI 0.00), and do not reach consensus for benign impact either — PP3 and BP4 are not met.
ClinVar classification is conflicting: two clinical laboratories report Uncertain Significance and one reports Pathogenic. No expert panel review is available. PP5 is not met due to conflicting interpretations, and BP6 is not met as no submitter classifies the variant as Benign.
Several criteria (PS3, PS4) could not be fully assessed because variant-specific evidence from cited publications could not be confirmed without full-text access. PMID:27345172 ('Distinct mutations at the same positions of STAT3 cause either loss or gain of function') is of particular relevance for functional evidence but has no abstract or full-text available in the evidence packet.
With 1 moderate criterion (PM1) and 1 supporting criterion (PM2) met, and no benign criteria met, the variant does not reach the Likely Pathogenic threshold (requires at least 1 strong + 1–2 moderate, or 3 moderate, or 2 moderate + 2 supporting). The variant is classified as a Variant of Uncertain Significance (VUS) according to generic ACMG/AMP 2015 combination rules.
No criteria match.
Met · 2
PM1 Moderatec.1940A>T (p.Asn647Ile) is located in the STAT3 Src homology 2 (SH2) domain (UniProt residues 583–688). The SH2 domain is a well-established mutational hotspot where numerous pathogenic missense variants have been documented in both germline hyper-IgE syndrome and somatic lymphoproliferative disorders. Multiple publications describe clustering of disease-associated missense mutations in the STAT3 SH2 domain. Details ▾Hide ▴
Evidence considered
- UniProt SH2 domain annotation: residues 583–688. PMID:22859607 reports SH2 domain (exons 20-21) as site of recurrent mutations. Position N647 within SH2 domain confirmed.
Still missing
- Formal PM1 domain-level benign vs. pathogenic count per ClinGen SVI recommendations not performed.
Sources
PM2 SupportingNM_139276.2:c.1940A>T is absent from gnomAD v2.1 (0/251,490 alleles) and extremely rare in gnomAD v4.1 (2/1,614,212 alleles; AF=1.24×10⁻⁶; grpmax FAF=2.8×10⁻⁷). Both are well below the 0.1% PM2 threshold. The variant is also absent from gnomAD-Canada. Details ▾Hide ▴
Evidence considered
- gnomAD v2.1: 0/251
- 490 (0.0%). gnomAD v4.1: 2/1
- 614
- 212 (AF=1.24×10⁻⁶). gnomAD-Canada: absent.
Sources
Not met · 15 · evaluated, threshold not reached
PS2 No report of de novo occurrence with confirmed maternity and paternity was identified for NM_139276.2:c.1940A>T in any ClinVar submission or reviewed literature. Details ▾Hide ▴
Evidence considered
- ClinVar submissions for this variant do not report de novo origin with confirmed parentage.
Still missing
- De novo case with confirmed parentage would be required to apply PS2.
Sources
PS4 PS4 requires that prevalence of the variant in affected individuals is significantly increased compared to controls. While gnomAD shows extreme rarity (2/1,614,212 alleles in v4.1), no variant-specific case counts in a defined germline disease cohort (e.g., hyper-IgE syndrome or STAT3-related immunodeficiency) were confirmed from full-text review. The 28 somatic occurrences in COSMIC are not informative for germline PS4. Without confirmed proband counts from the literature, PS4 cannot be applied. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 2/1
- 614
- 212 alleles (AF=1.24e-06). COSMIC: 28 somatic occurrences. No confirmed germline case counts from full-text review.
Still missing
- Confirmed proband counts from hyper-IgE syndrome or STAT3-related disease cohorts needed. Full-text review of PMID:27345172
- PMID:20301786 may yield case counts.
Sources
PM6 PM6 requires a de novo observation without confirmation of both maternity and paternity. No de novo report, with or without confirmed parentage, was identified for NM_139276.2:c.1940A>T in ClinVar submissions or reviewed literature. Details ▾Hide ▴
Evidence considered
- ClinVar submissions do not report de novo origin.
Still missing
- Any de novo observation
- even unconfirmed
- would need to be identified to apply PM6.
Sources
PP1 PP1 requires cosegregation of the variant with disease in multiple affected family members. No published pedigree with cosegregation data for NM_139276.2:c.1940A>T was identified. Details ▾Hide ▴
Evidence considered
- No segregation data found in ClinVar submissions or literature abstracts.
Still missing
- Cosegregation data from multi-generational families with hyper-IgE syndrome would be needed.
Sources
2030178627345172
PP3 PP3 requires multiple lines of computational evidence supporting a deleterious effect. REVEL score is 0.359 (below commonly used thresholds of ≥0.5–0.75 for pathogenic prediction), BayesDel is −0.126 (benign-leaning), and SpliceAI shows no splice impact (max delta = 0.00). In silico predictors do not reach consensus supporting a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL=0.359. BayesDel=−0.126. SpliceAI max delta=0.00. No consensus supporting pathogenicity.
Sources
PP5 PP5 requires a reputable source (e.g., clinical laboratory with expert review) to have classified the variant as pathogenic. ClinVar shows conflicting interpretations: two submitters classify as Uncertain Significance (LabCorp, SCV001737716; Labcorp Genetics, SCV004589843) and one as Pathogenic (CeGaT, SCV001371123). None are from an expert panel. The conflicting classifications, with the majority reporting VUS, preclude PP5 application. Details ▾Hide ▴
Evidence considered
- ClinVar: 2 VUS (LabCorp
- Labcorp Genetics) + 1 Pathogenic (CeGaT). No expert panel classification. Conflicting
- majority VUS.
Sources
BA1 BA1 requires an allele frequency >1% in a general population database. The variant is absent in gnomAD v2.1 and extremely rare in gnomAD v4.1 (AF=1.24×10⁻⁶; 2/1,614,212 alleles), far below the 1% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF=1.24×10⁻⁶
- well below 1% BA1 threshold.
Sources
BS1 BS1 requires an allele frequency >0.3% in a general population database. The variant is absent in gnomAD v2.1 and extremely rare in gnomAD v4.1 (AF=1.24×10⁻⁶), far below the 0.3% threshold. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1 AF=1.24×10⁻⁶
- well below 0.3% BS1 threshold.
Sources
BS2 BS2 requires observation of the variant in a healthy adult individual for a fully penetrant disorder. The two alleles observed in gnomAD v4.1 are from exome data of individuals with unknown phenotype and cannot be confirmed as healthy adult carriers. No other healthy adult observation is documented. Details ▾Hide ▴
Evidence considered
- gnomAD v4.1: 2 alleles
- phenotypes unknown. Cannot confirm healthy adult status.
Still missing
- Confirmation that gnomAD carriers are healthy adults without STAT3-related disease.
Sources
BS3 BS3 requires well-established in vitro/in vivo functional studies showing no damaging effect on the gene product. Available evidence suggests the opposite: OncoKB annotates this variant as 'Likely Oncogenic' (gain-of-function), and published functional studies of STAT3 SH2 domain mutations (PMID:22859607) describe altered STAT3 activation and gene deregulation. No evidence of normal function for N647I was identified. BS3 is not met. Details ▾Hide ▴
Evidence considered
- OncoKB: Likely Oncogenic. PMID:22859607: SH2 domain mutations associated with abnormal STAT3 activation. No evidence of preserved/normal function.
Sources
BS4 BS4 requires lack of segregation of the variant with disease in affected family members. No published pedigree with non-segregation data was identified for NM_139276.2:c.1940A>T. Details ▾Hide ▴
Evidence considered
- No non-segregation data identified in ClinVar or literature.
Still missing
- A family where an affected member lacks the variant (or an unaffected member carries it) would be needed.
BP1 BP1 applies to a missense variant in a gene where truncating variants are the primary mechanism of disease. STAT3-related hyper-IgE syndrome (autosomal dominant) is caused by dominant-negative missense mutations in the SH2 and DNA-binding domains, not by truncating/haploinsufficiency variants. The primary disease mechanism for STAT3 germline disorders involves missense variants, so BP1 does not apply. Details ▾Hide ▴
Evidence considered
- STAT3 hyper-IgE syndrome mechanism is dominant-negative missense
- not haploinsufficiency from truncating variants.
Sources
20301786
BP2 BP2 requires observation of the variant in trans with a known pathogenic variant in a gene for a fully penetrant dominant disorder. No individual carrying NM_139276.2:c.1940A>T in trans with a known pathogenic STAT3 variant has been reported. Details ▾Hide ▴
Evidence considered
- No trans observation with pathogenic STAT3 variant identified.
Still missing
- A healthy individual with N647I in trans with a pathogenic STAT3 variant would be needed.
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on the gene product. REVEL score is 0.359 (indeterminate), BayesDel is −0.126 (benign-leaning but not strongly so), and SpliceAI delta is 0.00. While BayesDel is slightly negative and SpliceAI shows no splice effect, REVEL does not strongly support benign impact and a consensus of benign prediction across tools is absent. Details ▾Hide ▴
Evidence considered
- REVEL=0.359 (indeterminate). BayesDel=−0.126 (benign-leaning). SpliceAI=0.00. No consensus benign prediction across tools.
Sources
BP6 BP6 requires a reputable source to classify the variant as benign. ClinVar shows two submissions as Uncertain Significance and one as Pathogenic; no submitter has classified the variant as Benign or Likely Benign. Details ▾Hide ▴
Evidence considered
- ClinVar: 2 VUS + 1 Pathogenic. No Benign or Likely Benign classification from any submitter.
Sources
Not assessed · 5 · no assessment recorded
PS1 PS1 requires a different nucleotide change at the same codon leading to the same missense change (N647I) that has been previously classified as pathogenic. No such alternate nucleotide variant was identified in the available evidence. Details ▾Hide ▴
Evidence considered
- No alternate nucleotide change to p.Asn647I identified in ClinVar or publications.
Still missing
- Comprehensive search for alternate nucleotide variants at codon 647 encoding N647I.
PS3 Well-established in vitro/in vivo functional studies are required for PS3. Several papers (PMID:22859607, PMID:27345172, PMID:31717342) discuss STAT3 SH2 domain functional characterization, but full-text could not be accessed to confirm variant-specific functional data for p.Asn647Ile (N647I). Abstract-level evidence from PMID:22859607 describes STAT3 mutations in SH2 domain affecting activation and gene regulation, but does not name N647I specifically. OncoKB annotates this variant as 'Likely Oncogenic' in somatic context, but this does not substitute for germline PS3 evidence. Details ▾Hide ▴
Evidence considered
- OncoKB annotation: Likely Oncogenic (somatic context). Abstract-level functional descriptions in PMID:22859607
- PMID:31717342 lack variant-specific confirmation.
Still missing
- Full-text review of PMID:27345172 ('Distinct mutations at the same positions of STAT3 cause either loss or gain of function')
- PMID:22859607
- PMID:31717342 needed to confirm N647I-specific functional data.
Sources
PP2 PP2 requires a missense variant in a gene with a low rate of benign missense variation where missense variants are a common mechanism of disease. STAT3 has a dual role: dominant-negative missense mutations in the SH2 domain cause hyper-IgE syndrome (germline), while gain-of-function missense mutations drive somatic malignancies. The gene-level benign missense constraint metrics were not evaluated. This criterion requires a dedicated Z-score/missense constraint analysis not available in the evidence packet. Details ▾Hide ▴
Evidence considered
- STAT3 has disease-associated missense variants but gene-level benign missense constraint not formally evaluated.
Still missing
- Gene-level missense constraint metrics (e.g.
- gnomAD missense Z-score
- o/e) needed to determine PP2 eligibility.
PP4 PP4 requires that the patient's phenotype or family history is highly specific for the disease associated with the gene. No patient phenotype information was available in the case evidence packet. Details ▾Hide ▴
Evidence considered
- No proband phenotype data available.
Still missing
- Proband clinical phenotype and family history required to assess PP4.
BP5 BP5 requires an alternate molecular basis for disease in a case where the variant was observed. No case with an alternate molecular cause was identified in the available evidence. Details ▾Hide ▴
Evidence considered
- No case with alternate molecular cause identified.
Still missing
- A case carrying N647I with a confirmed alternate genetic cause for the phenotype would be needed.
Not applicable · 4· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 N/APVS1 applies to null variants (nonsense, frameshift, canonical splice ±1,2). NM_139276.2:c.1940A>T is a missense variant (p.Asn647Ile) and does not fall into any PVS1 null-variant bucket per ClinGen SVI PVS1 recommendations (PMC6185798). Details ▾Hide ▴
Evidence considered
- Missense variant in exon 21
- no canonical splice disruption
- PVS1 gene gate is 'eligible' for STAT3 but variant class disqualifies.
Sources
PM5 N/ANo alternate missense change at codon 647 with a pathogenic classification was identified as a PM5 comparator. The automated PM5 candidate harvest returned zero same-residue candidates. Details ▾Hide ▴
Evidence considered
- pm5_candidates.json: no same-residue comparator variants identified.
BP7 N/ABP7 applies only to synonymous (silent) variants without predicted splice impact. NM_139276.2:c.1940A>T is a missense variant (p.Asn647Ile) and is not synonymous. Details ▾Hide ▴
PS5 N/APS5 is not part of the standard ACMG/AMP 2015 criteria (PMID:25741868). The related criterion PS1 (same amino acid change from a different nucleotide) was separately assessed. Details ▾Hide ▴
Evidence considered
- PS5 not defined in generic ACMG/AMP 2015 framework.
Identifiers
- Gene
- STAT3
- Transcript
- NM_139276.2
- Coding (HGVS c.)
- NM_139276.2:c.1940A>T
- Protein (HGVS p.)
- NP_644805.1:p.(Asn647Ile)
- GRCh38
- chr17:42322443 T>A
- GRCh37
- chr17:40474461 T>A
- ClinVar
- 932423, 2429308
- COSMIC
- COSV52882818
Gene diagram
Every interpreted variant in STAT3, mapped onto the exon structure of NM_139276.2. Select a row to find it on the plot.
STAT3NM_139276.2
Fetching transcript structure from UCSC…
Exons
—
Transcript span
—
Strand
—
Variants mapped
—
Source
UCSC ncbiRefSeqCurated
All variants in STAT3
—
Select a row to find it on the plot; use the link to open its page.
| Protein | Location | Classification | Link |
|---|
gnomAD v4.1
2 / 1,614,212 alleles
AF 1.24e-06 · 0 homozygotes · FAF 2.8e-07
gnomAD v2.1
0 / 251,490 alleles
AF 0 · 0 homozygotes
gnomAD-Canada v1.0
Allele count data not recorded
By genetic ancestry
gnomAD v4.1
AF 1.2e-06 · 2 / 1,614,212 alleles · 0 hom · FAF 2.8e-07
| European (non-Finnish)2 / 1,180,028 | 1.7e-06 |
0 alternate alleles recorded in 9 other groups: Remaining individuals, Admixed American, European (Finnish), Amish, East Asian, Middle Eastern, South Asian, Ashkenazi Jewish, African/African American.
gnomAD v2.1
AF 0 · 0 / 251,490 alleles · 0 hom
No alternate alleles recorded in the displayed ancestry groups.
Statements
gnomAD v4.1
This variant is present in gnomAD v4.1 (AF= 1.23899e-06; MAF= 0.00012%, 2/1614212 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.69488e-06; MAF= 0.00017%, 2/1180028 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0; MAF= 0.00000%, 0/251490 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/16256 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
SpliceAI and Pangolin
Other predictors
- REVEL
- 0.359
- BayesDel
- -0.126
How the predictions were used
PP3 PP3 requires multiple lines of computational evidence supporting a deleterious effect. REVEL score is 0.359 (below commonly used thresholds of ≥0.5–0.75 for pathogenic prediction), BayesDel is −0.126 (benign-leaning), and SpliceAI shows no splice impact (max delta = 0.00). In silico predictors do not reach consensus supporting a deleterious effect. Details ▾Hide ▴
Evidence considered
- REVEL=0.359. BayesDel=−0.126. SpliceAI max delta=0.00. No consensus supporting pathogenicity.
Sources
BP4 BP4 requires multiple lines of computational evidence suggesting no impact on the gene product. REVEL score is 0.359 (indeterminate), BayesDel is −0.126 (benign-leaning but not strongly so), and SpliceAI delta is 0.00. While BayesDel is slightly negative and SpliceAI shows no splice effect, REVEL does not strongly support benign impact and a consensus of benign prediction across tools is absent. Details ▾Hide ▴
Evidence considered
- REVEL=0.359 (indeterminate). BayesDel=−0.126 (benign-leaning). SpliceAI=0.00. No consensus benign prediction across tools.
Sources
BP7 N/ABP7 applies only to synonymous (silent) variants without predicted splice impact. NM_139276.2:c.1940A>T is a missense variant (p.Asn647Ile) and is not synonymous. Details ▾Hide ▴
Statement
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.359. BayesDel score = -0.125529.
8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata. None of the listed paper records explicitly indicates that the variant is named.
Recorded publications
-
PMID 27345172 ↗Distinct mutations at the same positions of STAT3 cause either loss or gain of function.Chandrasekaran P et al. · 2016No paper-specific finding is recorded.
-
PMID 22859607 ↗STAT3 mutations unify the pathogenesis of chronic lymphoproliferative disorders of NK cells and T-cell large granular lymphocyte leukemia.Jerez A et al. · 2012No paper-specific finding is recorded.
-
PMID 31002364 ↗JAK3/STAT3 oncogenic pathway and PRDM1 expression stratify clinicopathologic features of extranodal NK/T‑cell lymphoma, nasal type.Liu J et al. · 2019No paper-specific finding is recorded.
-
PMID 31278738 ↗Molecular Genetics in the Diagnosis and Biology of Lymphoid Neoplasms.Lim MS et al. · 2019No paper-specific finding is recorded.
-
PMID 31717342 ↗Structural Implications of STAT3 and STAT5 SH2 Domain Mutations.de Araujo ED et al. · 2019No paper-specific finding is recorded.
-
PMID 32273478 ↗Genetic lesions in MYC and STAT3 drive oncogenic transcription factor overexpression in plasmablastic lymphoma.Garcia-Reyero J et al. · 2021No paper-specific finding is recorded.
-
PMID 33579790 ↗Oncogenetic landscape of lymphomagenesis in coeliac disease.Cording S et al. · 2022No paper-specific finding is recorded.
-
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
2 / 1,614,212 recorded alleles
Open source ↗
gnomAD v2.1
Captured gnomAD v2.1 source record
Open source ↗
SpliceAI Lookup
Recorded maximum delta 0.000
Open source ↗
ClinVar
2 Uncertain significance · 1 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 ↗
All source links
- ClinVar ↗www.ncbi.nlm.nih.gov/clinvar/variation/932423/
- gnomAD v2.1 ↗gnomad.broadinstitute.org/variant/17-40474461-T-A?dataset=gnomad_r2_1
- gnomAD v4.1 ↗gnomad.broadinstitute.org/variant/chr17-42322443-T-A?dataset=gn…
- gnomAD-Canada ↗http://192.168.4.76:8001/variant/17-42322443-T-A
- SpliceAI Lookup ↗spliceailookup.broadinstitute.org/#variant=NM_139276.2%3Ac.1940…
- OncoKB ↗www.oncokb.org/gene/STAT3/N647I
- COSMIC ↗cancer.sanger.ac.uk/cosmic/mutation/overview?id=121819271
- 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
This variant is present in gnomAD v4.1 (AF= 1.23899e-06; MAF= 0.00012%, 2/1614212 alleles, homozygotes = 0) and has highest observed frequency in the European (non-Finnish) population (AF= 1.69488e-06; MAF= 0.00017%, 2/1180028 alleles, homozygotes = 0); grpmax FAF= 2.8e-07.
gnomAD v2.1
This variant is present in gnomAD v2.1 (AF= 0; MAF= 0.00000%, 0/251490 alleles, homozygotes = 0) and has highest observed frequency in the African/African American population (AF= 0; MAF= 0.00000%, 0/16256 alleles, homozygotes = 0).
gnomAD-Canada
Absent from gnomAD-Canada v1.0.
ClinVar
This variant has been reported in ClinVar as Uncertain significance (2 clinical laboratories) and as Pathogenic (1 clinical laboratory). (ClinVarID = 932423)
In silico
SpliceAI predicts no significant splice impact for this variant (max delta score = 0.00). REVEL score = 0.359. BayesDel score = -0.125529.
Functional
OncoKB identified variant-specific curated literature and context relevant to functional review; biological-effect context: Likely Gain-of-function; curated oncogenicity label: Likely Oncogenic.
Somatic
This variant does not lie in a statistically significant hotspot. This variant has previously been reported in somatic cancers (COSMIC; COSV52882818, n = 28 times).
Cancer Hotspots
This variant does not lie in a statistically significant hotspot.