NM_000215.4(JAK3):c.2272C>T (p.Gln758Ter) AND T-B+ severe combined immunodeficiency due to JAK3 deficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 21, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003510611.2

Allele description [Variation Report for NM_000215.4(JAK3):c.2272C>T (p.Gln758Ter)]

NM_000215.4(JAK3):c.2272C>T (p.Gln758Ter)

Gene:
JAK3:Janus kinase 3 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
19p13.11
Genomic location:
Preferred name:
NM_000215.4(JAK3):c.2272C>T (p.Gln758Ter)
HGVS:
  • NC_000019.10:g.17834649G>A
  • NG_007273.1:g.18343C>T
  • NM_000215.4:c.2272C>TMANE SELECT
  • NP_000206.2:p.Gln758Ter
  • NP_000206.2:p.Gln758Ter
  • LRG_77t1:c.2272C>T
  • LRG_77:g.18343C>T
  • LRG_77p1:p.Gln758Ter
  • NC_000019.9:g.17945458G>A
  • NM_000215.3:c.2272C>T
Protein change:
Q758*
Molecular consequence:
  • NM_000215.4:c.2272C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
T-B+ severe combined immunodeficiency due to JAK3 deficiency
Synonyms:
SCID, T CELL-NEGATIVE, B CELL-POSITIVE, NK CELL-NEGATIVE; Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-positive, NK cell-negative; SCID, autosomal recessive, T-negative/B-positive type
Identifiers:
MONDO: MONDO:0010938; MedGen: C1833275; Orphanet: 35078; OMIM: 600802

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004365618Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 21, 2023) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

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

Citations

PubMed

Mutation of Jak3 in a patient with SCID: essential role of Jak3 in lymphoid development.

Russell SM, Tayebi N, Nakajima H, Riedy MC, Roberts JL, Aman MJ, Migone TS, Noguchi M, Markert ML, Buckley RH, O'Shea JJ, Leonard WJ.

Science. 1995 Nov 3;270(5237):797-800.

PubMed [citation]
PMID:
7481768

Eleven novel JAK3 mutations in patients with severe combined immunodeficiency-including the first patients with mutations in the kinase domain.

Mella P, Schumacher RF, Cranston T, de Saint Basile G, Savoldi G, Notarangelo LD.

Hum Mutat. 2001 Oct;18(4):355-6.

PubMed [citation]
PMID:
11668621
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004365618.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Gln758*) in the JAK3 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in JAK3 are known to be pathogenic (PMID: 7481768, 11668621). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with JAK3-related conditions. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024