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NM_139276.3(STAT3):c.2082T>A (p.His694Gln) AND multiple conditions

Clinical significance:Uncertain significance (Last evaluated: Dec 8, 2021)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001070774.4

Allele description [Variation Report for NM_139276.3(STAT3):c.2082T>A (p.His694Gln)]

NM_139276.3(STAT3):c.2082T>A (p.His694Gln)

Gene:
STAT3:signal transducer and activator of transcription 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
17q21.2
Genomic location:
Preferred name:
NM_139276.3(STAT3):c.2082T>A (p.His694Gln)
HGVS:
  • NC_000017.11:g.42322301A>T
  • NG_007370.1:g.71195T>A
  • NM_001369512.1:c.2082T>A
  • NM_001369513.1:c.2082T>A
  • NM_001369514.1:c.2082T>A
  • NM_001369516.1:c.2082T>A
  • NM_001369517.1:c.2082T>A
  • NM_001369518.1:c.2082T>A
  • NM_001369519.1:c.2082T>A
  • NM_001369520.1:c.2082T>A
  • NM_001384984.1:c.1998T>A
  • NM_001384985.1:c.2004T>A
  • NM_001384986.1:c.2097T>A
  • NM_001384987.1:c.2061T>A
  • NM_001384988.1:c.2082T>A
  • NM_001384989.1:c.1986T>A
  • NM_001384990.1:c.2097T>A
  • NM_001384991.1:c.2055T>A
  • NM_001384992.1:c.2022T>A
  • NM_001384993.1:c.2082T>A
  • NM_003150.4:c.2082T>A
  • NM_139276.3:c.2082T>AMANE SELECT
  • NM_213662.2:c.2082T>A
  • NP_001356441.1:p.His694Gln
  • NP_001356442.1:p.His694Gln
  • NP_001356443.1:p.His694Gln
  • NP_001356445.1:p.His694Gln
  • NP_001356446.1:p.His694Gln
  • NP_001356447.1:p.His694Gln
  • NP_001356448.1:p.His694Gln
  • NP_001356449.1:p.His694Gln
  • NP_001371913.1:p.His666Gln
  • NP_001371914.1:p.His668Gln
  • NP_001371915.1:p.His699Gln
  • NP_001371916.1:p.His687Gln
  • NP_001371917.1:p.His694Gln
  • NP_001371918.1:p.His662Gln
  • NP_001371919.1:p.His699Gln
  • NP_001371920.1:p.His685Gln
  • NP_001371921.1:p.His674Gln
  • NP_001371922.1:p.His694Gln
  • NP_003141.2:p.His694Gln
  • NP_644805.1:p.His694Gln
  • NP_644805.1:p.His694Gln
  • NP_998827.1:p.His694Gln
  • LRG_112t1:c.2082T>A
  • LRG_112:g.71195T>A
  • LRG_112p1:p.His694Gln
  • NC_000017.10:g.40474319A>T
  • NM_139276.2:c.2082T>A
Protein change:
H662Q
Links:
dbSNP: rs139701269
NCBI 1000 Genomes Browser:
rs139701269
Molecular consequence:
  • NM_001369512.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369513.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369514.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369516.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369517.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369518.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369519.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001369520.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384984.1:c.1998T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384985.1:c.2004T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384986.1:c.2097T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384987.1:c.2061T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384988.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384989.1:c.1986T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384990.1:c.2097T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384991.1:c.2055T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384992.1:c.2022T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001384993.1:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003150.4:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_139276.3:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_213662.2:c.2082T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Hyper-IgE recurrent infection syndrome 1
Synonyms:
Hyperimmunoglobulin E recurrent infection syndrome, autosomal dominant; HIES autosomal dominant; AD hyperimmunoglobulin E syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0007818; MedGen: C4721531; Orphanet: 2314; OMIM: 147060
Name:
STAT3 gain of function
Identifiers:
MedGen: C4288261

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV001236042Invitaecriteria provided, single submitter
Uncertain significance
(Dec 8, 2021)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Systematic STAT3 sequencing in patients with unexplained cytopenias identifies unsuspected large granular lymphocytic leukemia.

Morgan EA, Lee MN, DeAngelo DJ, Steensma DP, Stone RM, Kuo FC, Aster JC, Gibson CJ, Lindsley RC.

Blood Adv. 2017 Sep 26;1(21):1786-1789. doi: 10.1182/bloodadvances.2017011197. No abstract available.

PubMed [citation]
PMID:
29296824
PMCID:
PMC5728102

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV001236042.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces histidine, which is basic and polar, with glutamine, which is neutral and polar, at codon 694 of the STAT3 protein (p.His694Gln). This variant is present in population databases (rs139701269, gnomAD 0.01%). This missense change has been observed in individual(s) with leukocytosis and splenomegaly (PMID: 29296824). ClinVar contains an entry for this variant (Variation ID: 633187). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt STAT3 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 24, 2022

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