NM_000536.4(RAG2):c.303T>A (p.Asn101Lys) AND Severe combined immunodeficiency disease

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Oct 24, 2025
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:: RCV006454313.1

Allele description [Variation Report for NM_000536.4(RAG2):c.303T>A (p.Asn101Lys)]

NM_000536.4(RAG2):c.303T>A (p.Asn101Lys)

Gene:

RAG2:recombination activating 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

11p12

Genomic location:

Preferred name:

NM_000536.4(RAG2):c.303T>A (p.Asn101Lys)

HGVS:

NC_000011.10:g.36593866A>T
NG_007573.1:g.9371T>A
NG_033154.1:g.4374A>T
NM_000536.4:c.303T>AMANE SELECT
NM_001243785.2:c.303T>A
NM_001243786.2:c.303T>A
NP_000527.2:p.Asn101Lys
NP_000527.2:p.Asn101Lys
NP_001230714.1:p.Asn101Lys
NP_001230715.1:p.Asn101Lys
LRG_99t1:c.303T>A
LRG_99:g.9371T>A
LRG_99p1:p.Asn101Lys
NC_000011.9:g.36615416A>T
NM_000536.2:c.303T>A

Protein change:

N101K

Links:

dbSNP: rs2133315445

Molecular consequence:

NM_000536.4:c.303T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243785.2:c.303T>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001243786.2:c.303T>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Severe combined immunodeficiency disease
Synonyms:: Severe combined immunodeficiency; Severe Combined Immune Deficiency
Identifiers:: MONDO: MONDO:0015974; MeSH: D016511; MedGen: C0085110; Human Phenotype Ontology: HP:0004430

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV005203425	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely pathogenic (Oct 24, 2025)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV005203425

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely pathogenic
(Oct 24, 2025)

germline

clinical testing

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

Citation Link

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

Clinical, Immunological, and Molecular Features of Severe Combined Immune Deficiency: A Multi-Institutional Experience From India.

Vignesh P, Rawat A, Kumrah R, Singh A, Gummadi A, Sharma M, Kaur A, Nameirakpam J, Jindal A, Suri D, Gupta A, Khadwal A, Saikia B, Minz RW, Sharma K, Desai M, Taur P, Gowri V, Pandrowala A, Dalvi A, Jodhawat N, Kambli P, et al.

Front Immunol. 2020;11:619146. doi: 10.3389/fimmu.2020.619146.

PubMed [citation]

PMID:: 33628209
PMCID:: PMC7897653

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV005203425.3

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

Description

Variant summary: RAG2 c.303T>A (p.Asn101Lys) results in a non-conservative amino acid change in the encoded protein sequence. Algorithms developed to predict the effect of missense changes on protein structure and function all suggest that this variant is likely to be disruptive. The variant was absent in 251442 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.303T>A has been observed in one individual affected with features of Severe Combined Immunodeficiency (Vignesh_2021, internal data). These data suggests that this variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 33628209). ClinVar contains an entry for this variant (Variation ID: 2087156). Based on the evidence outlined above, the variant was classified as likely pathogenic.

#	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: Apr 12, 2026

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