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_001243786.2:c.1A>G

CA380145381

624606 (ClinVar)

Gene: RAG2 (HGNC:5897)

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

Inheritance Mode: Autosomal recessive inheritance

UUID: 8183c0fe-3833-4873-9920-3ead36ab5186

Approved on: 2024-06-14

Published on: 2024-06-14

HGVS expressions

NM_001243786.2:c.1A>G

NC_000011.10:g.36594168T>C

CM000673.2:g.36594168T>C

NC_000011.9:g.36615718T>C

CM000673.1:g.36615718T>C

NC_000011.8:g.36572294T>C

NG_007573.1:g.9069A>G

NG_033154.1:g.4676T>C

ENST00000527033.6:c.1A>G

ENST00000529083.2:c.1A>G

ENST00000532616.2:c.1A>G

ENST00000311485.8:c.1A>G

ENST00000311485.7:c.1A>G

ENST00000524423.1:n.131+3934A>G

ENST00000527033.5:c.1A>G

ENST00000529083.1:c.1A>G

ENST00000532616.1:c.1A>G

ENST00000618712.4:c.1A>G

NM_000536.3:c.1A>G

NM_001243785.1:c.1A>G

NM_001243786.1:c.1A>G

NM_000536.4:c.1A>G

NM_001243785.2:c.1A>G

Uncertain Significance

PP4 PM2_Supporting PVS1_Supporting PM1_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.1A>G is a missense variant predicted to cause substitution of Methionine by Valine at amino acid 1 (p.Met1Val). This sequence change affects the initiator methionine of the RAG2 mRNA. The next possible initiation codon is at codon 5. This region does not contain known pathogenic/likely pathogenic variants (PVS1_Supporting). This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting). The variant is absent in gnomAD v4 (PM2_supporting). Female with SCID (0.5 pt.), genome sequencing conducted (0.5 pt.)& T-B-NK+ lymphocyte subset profile (0.5 pt.) (Total :1.5 pts) (PP4 met) (PMID: 31031743). The patient was found compound heterozygous for c.1A>G; p.M1V and c.1403_1406delATCT (not evaluated by SCID VCEP yet) (PMID: 31031743) (PM3 not evaluated). 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: PVS1_Supporting,PM1_supporting, PM2_supporting,PP4 met(VCEP specifications version 1).

PP4

Female with SCID (0.5 pt.), genome sequencing conducted (0.5 pt.)& T-B-NK+ lymphocyte subset profile (0.5 pt.) (Total :1.5 pts) (PP4 met) PMID: 31031743

PM2_Supporting

The variant is absent in gnomAD v4 (PM2_supporting).

PVS1_Supporting

This sequence change affects the initiator methionine of the RAG2 mRNA. The next possible initiation codon is at codon 5. This region does not contain known pathogenic/likely pathogenic variants (PVS1_Supporting).

PM1_Supporting

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

Curation History

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