Variant: NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)

CA5950260

418449 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: cfafc8ac-46c0-4aff-a6b0-3e969310fc93

Approved on: 2024-02-26

Published on: 2024-02-26

HGVS expressions

NM_000448.3:c.2442G>T
NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)
NC_000011.10:g.36575746G>T
CM000673.2:g.36575746G>T
NC_000011.9:g.36597296G>T
CM000673.1:g.36597296G>T
NC_000011.8:g.36553872G>T
NG_007528.1:g.12734G>T
ENST00000697713.1:c.2442G>T
ENST00000697714.1:c.2442G>T
ENST00000697715.1:c.2442G>T
ENST00000299440.6:c.2442G>T
ENST00000299440.5:c.2442G>T
ENST00000524423.1:n.357C>A
ENST00000534663.1:c.2442G>T
NM_000448.2:c.2442G>T
NM_001377277.1:c.2442G>T
NM_001377278.1:c.2442G>T
NM_001377279.1:c.2442G>T
NM_001377280.1:c.2442G>T

Uncertain Significance

• Met criteria codes: PM2_Supporting PM1_Supporting

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

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000448.3(RAG1):c.2442G>T is a missense variant predicted to cause substitution of Glutamic Acid by Aspartic Acid at amino acid 814 (p.Glu814Asp). This missense variant is located in the core domain (amino acids 387-1011) (PM1_Supporting). The filtering allele frequency (the upper threshold of the 95% CI of 3/44724) of the c.2442G>T variant in RAG1 is 0.00001779 for Admixed American chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.000102) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to RAG1 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: PM1_Supporting,PM2_Supporting(VCEP specifications version 1).

Met criteria codes

• PM2_Supporting: The filtering allele frequency (the upper threshold of the 95% CI of 3/44724) of the c.2442G>T variant in RAG1 is 0.00001779 for Admixed American chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.000102) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).
• PM1_Supporting: This missense variant is located in the core domain (amino acids 387-1011) (PM1_Supporting).