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_000448.3(RAG1):c.2814T>G (p.Tyr938Ter)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA122880

13141 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 5eb328af-1683-4667-8e5c-50a71d2d9036

Approved on: 2024-03-04

Published on: 2024-03-04

HGVS expressions

NM_000448.3:c.2814T>G

NM_000448.3(RAG1):c.2814T>G (p.Tyr938Ter)

NC_000011.10:g.36576118T>G

CM000673.2:g.36576118T>G

NC_000011.9:g.36597668T>G

CM000673.1:g.36597668T>G

NC_000011.8:g.36554244T>G

NG_007528.1:g.13106T>G

ENST00000697713.1:c.2814T>G

ENST00000697714.1:c.2814T>G

ENST00000697715.1:c.2814T>G

ENST00000299440.6:c.2814T>G

ENST00000299440.5:c.2814T>G

ENST00000524423.1:n.132-147A>C

ENST00000534663.1:c.2789+25T>G

NM_000448.2:c.2814T>G

NM_001377277.1:c.2814T>G

NM_001377278.1:c.2814T>G

NM_001377279.1:c.2814T>G

NM_001377280.1:c.2814T>G

Likely Pathogenic

PVS1 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 RAG1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

The c.2814T>G (p.Tyr938Ter) (NM_000448.3) variant in RAG1 is a nonsense variant that may cause a premature stop codon that is predicted to escape nonsense-mediated decay. However, it is predicted to truncate part of the core region (between aa 387-1011) critical to the function of the protein (PVS1 Met).The variant is absent in gnomAD v4 (PM2_supporting). In summary, this variant meets the criteria to be classified as a likely pathogenic variant for autosomal recessive severe combined immunodeficiency due to RAG1 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM2_Supporting,PVS1 Met (VCEP specifications version 1).

PVS1

PM2_Supporting

The variant is absent in gnomAD v4 (PM2_supporting).

Curation History

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