Variant: NM_000536.4(RAG2):c.25A>G (p.Ser9Gly)

CA380145206

1349574 (ClinVar)

Gene: RAG2

Condition: recombinase activating gene 2 deficiency

Inheritance Mode: Autosomal recessive inheritance

UUID: 1cc2b5eb-a08c-4bc6-aac5-2dcd5c47b2bb

Approved on: 2024-05-07

Published on: 2024-05-07

HGVS expressions

NM_000536.4:c.25A>G
NM_000536.4(RAG2):c.25A>G (p.Ser9Gly)
NC_000011.10:g.36594144T>C
CM000673.2:g.36594144T>C
NC_000011.9:g.36615694T>C
CM000673.1:g.36615694T>C
NC_000011.8:g.36572270T>C
NG_007573.1:g.9093A>G
NG_033154.1:g.4652T>C
ENST00000527033.6:c.25A>G
ENST00000529083.2:c.25A>G
ENST00000532616.2:c.25A>G
ENST00000311485.8:c.25A>G
ENST00000311485.7:c.25A>G
ENST00000524423.1:n.131+3958A>G
ENST00000527033.5:c.25A>G
ENST00000529083.1:c.25A>G
ENST00000618712.4:c.25A>G
NM_000536.3:c.25A>G
NM_001243785.1:c.25A>G
NM_001243786.1:c.25A>G
NM_001243785.2:c.25A>G
NM_001243786.2:c.25A>G

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 RAG2 Version 1.0.0

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000536.4(RAG2):c.25A>G is a missense variant predicted to cause substitution of Serine by Glycine at amino acid 9 (p.Ser9Gly).This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting).The highest population minor allele frequency in gnomAD v4 is 0.00003333 (2/60006) in Admixed American population 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).

Met criteria codes

• PM2_Supporting: The highest population minor allele frequency in gnomAD v4 is 0.00003333 (2/60006) in Admixed American population which is lower than the ClinGen SCID VCEP threshold (<0.0000588) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting).
• PM1_Supporting: This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting).