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NM_000536.4(RAG2):c.35T>C (p.Ile12Thr) AND Recombinase activating gene 2 deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Jun 10, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV004765335.1

Allele description [Variation Report for NM_000536.4(RAG2):c.35T>C (p.Ile12Thr)]

NM_000536.4(RAG2):c.35T>C (p.Ile12Thr)

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.35T>C (p.Ile12Thr)
Other names:
NM_000536.4(RAG2):c.35T>C; p.Ile12Thr
HGVS:
  • NC_000011.10:g.36594134A>G
  • NG_007573.1:g.9103T>C
  • NG_033154.1:g.4642A>G
  • NM_000536.4:c.35T>CMANE SELECT
  • NM_001243785.2:c.35T>C
  • NM_001243786.2:c.35T>C
  • NP_000527.2:p.Ile12Thr
  • NP_001230714.1:p.Ile12Thr
  • NP_001230715.1:p.Ile12Thr
  • LRG_99:g.9103T>C
  • NC_000011.9:g.36615684A>G
  • NM_000536.3:c.35T>C
Protein change:
I12T
Links:
dbSNP: rs146584017
NCBI 1000 Genomes Browser:
rs146584017
Molecular consequence:
  • NM_000536.4:c.35T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243785.2:c.35T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001243786.2:c.35T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Recombinase activating gene 2 deficiency
Synonyms:
RAG2 deficiency
Identifiers:
MONDO: MONDO:0000573; MedGen: CN257931

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV005375458ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen SCID ACMG Specifications RAG2 V1.0.0)		Uncertain Significance
(Jun 10, 2024) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV005375458.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000536.4(RAG2):c.35T>C is a missense variant predicted to cause substitution of Isoleucine by Threonine at amino acid 12 (p.Ile12Thr).This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting). The highest population minor allele frequency in gnomAD v4 is 0.001750 (151/75030) in African/African American population. (PM2_Supporting, BS1 and BA1 are not met). To our knowledge, this variant has not been reported in the literature in individuals affected with RAG2 related conditions or in functional studies. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to RAG2 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM1_supporting (VCEP specifications version 1).

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

Last Updated: Oct 26, 2024