NM_000215.4(JAK3):c.2105T>C (p.Leu702Pro) AND T-B+ severe combined immunodeficiency due to JAK3 deficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Sep 2, 2021
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:: RCV000792655.6

Allele description [Variation Report for NM_000215.4(JAK3):c.2105T>C (p.Leu702Pro)]

NM_000215.4(JAK3):c.2105T>C (p.Leu702Pro)

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.2105T>C (p.Leu702Pro)

HGVS:

NC_000019.10:g.17834946A>G
NG_007273.1:g.18046T>C
NM_000215.4:c.2105T>CMANE SELECT
NP_000206.2:p.Leu702Pro
NP_000206.2:p.Leu702Pro
LRG_77t1:c.2105T>C
LRG_77:g.18046T>C
LRG_77p1:p.Leu702Pro
NC_000019.9:g.17945755A>G
NM_000215.3:c.2105T>C

Protein change:

L702P

Links:

dbSNP: rs772117537

NCBI 1000 Genomes Browser:

rs772117537

Molecular consequence:

NM_000215.4:c.2105T>C - missense variant - [Sequence Ontology: SO:0001583]

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

Recent activity

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UI-H-EZ0-bao-g-18-0-UI.s1 NCI_CGAP_Ch1 Homo sapiens cDNA clone UI-H-EZ0-bao-g-18...
UI-H-EZ0-bao-g-18-0-UI.s1 NCI_CGAP_Ch1 Homo sapiens cDNA clone UI-H-EZ0-bao-g-18-0-UI 3', mRNA sequence
gi|24775503|gnl|dbEST|15133646|gb|C 52.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000931964	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Sep 2, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000931964

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Sep 2, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

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

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000931964.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

Description

This sequence change replaces leucine with proline at codon 702 of the JAK3 protein (p.Leu702Pro). The leucine residue is highly conserved and there is a moderate physicochemical difference between leucine and proline. This variant is present in population databases (rs772117537, ExAC 0.003%). This variant has not been reported in the literature in individuals affected with JAK3-related conditions. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). 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: Sep 29, 2024

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