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]

Link to SEPIO compliant JSON-LD document

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

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

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

PM2_Supporting PVS1

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).

PM2_Supporting

The variant is absent in gnomAD v4 (PM2_supporting).

PVS1

Approved on: 2024-03-04

Published on: 2024-03-04

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.