Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000536.4(RAG2):c.68A>G (p.Asn23Ser)

CA5950626

658239 (ClinVar)

Gene: RAG2 (HGNC:5897)

Condition: recombinase activating gene 2 deficiency (MONDO:0000573)

Inheritance Mode: Autosomal recessive inheritance

UUID: 0c7e064f-b844-4c8d-ae3c-8d79c1acc225

Approved on: 2024-05-01

Published on: 2024-05-01

HGVS expressions

NM_000536.4(RAG2):c.68A>G (p.Asn23Ser)

NM_000536.4:c.68A>G

NC_000011.10:g.36594101T>C

CM000673.2:g.36594101T>C

NC_000011.9:g.36615651T>C

CM000673.1:g.36615651T>C

NC_000011.8:g.36572227T>C

NG_007573.1:g.9136A>G

NG_033154.1:g.4609T>C

ENST00000527033.6:c.68A>G

ENST00000529083.2:c.68A>G

ENST00000532616.2:c.68A>G

ENST00000311485.8:c.68A>G

ENST00000311485.7:c.68A>G

ENST00000524423.1:n.131+4001A>G

ENST00000527033.5:c.68A>G

ENST00000529083.1:c.68A>G

ENST00000618712.4:c.68A>G

NM_000536.3:c.68A>G

NM_001243785.1:c.68A>G

NM_001243786.1:c.68A>G

NM_001243785.2:c.68A>G

NM_001243786.2:c.68A>G

Uncertain Significance

PM1_Supporting PM2_Supporting

Evidence Links 0

Expert Panel

Severe Combined Immunodeficiency Disease VCEP

Criteria Specification Information

Criteria Specification: ClinGen Severe Combined Immunodeficiency Disease Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for RAG2 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000536.4(RAG2):c.68A>G (p.Asn23Ser) is a missense variant predicted to cause substitution of Asparagine by Serine at amino acid 23.This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting). The filtering allele frequency (the upper threshold of the 95% CI of 11/1180018) of the c.68A>G variant in RAG2 is 0.000004550 for European (Non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0000588) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). 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, PM2_supporting (VCEP specifications version 1).

PM1_Supporting

This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting).

PM2_Supporting

The filtering allele frequency (the upper threshold of the 95% CI of 11/1180018) of the c.68A>G variant in RAG2 is 0.000004550 for European (Non-Finnish) chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.0000588) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.