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

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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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001236042	Invitae	criteria provided, single submitter Invitae Variant Classification Sherloc (09022015)	Uncertain significance (Dec 8, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 29296824, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001236042

Invitae

criteria provided, single submitter

Invitae Variant Classification Sherloc (09022015)

Uncertain significance
(Dec 8, 2021)

germline

clinical testing

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

Summary from all submissions

Help

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Jun 24, 2022

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