Evidence Repository - GenboreeKB

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_000536.4(RAG2):c.878A>G (p.Glu293Gly)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA5950510

256378 (ClinVar)

Gene: RAG2

Condition: recombinase activating gene 2 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 6911fcf3-20bc-4fc2-99cd-a3df948f8de8

Approved on: 2024-04-03

Published on: 2024-04-03

HGVS expressions

NM_000536.4:c.878A>G

NM_000536.4(RAG2):c.878A>G (p.Glu293Gly)

NC_000011.10:g.36593291T>C

CM000673.2:g.36593291T>C

NC_000011.9:g.36614841T>C

CM000673.1:g.36614841T>C

NC_000011.8:g.36571417T>C

NG_007573.1:g.9946A>G

NG_033154.1:g.3799T>C

ENST00000527033.6:c.878A>G

ENST00000529083.2:c.878A>G

ENST00000532616.2:c.878A>G

ENST00000311485.8:c.878A>G

ENST00000311485.7:c.878A>G

ENST00000524423.1:n.131+4811A>G

ENST00000618712.4:c.878A>G

NM_000536.3:c.878A>G

NM_001243785.1:c.878A>G

NM_001243786.1:c.878A>G

NM_001243785.2:c.878A>G

NM_001243786.2:c.878A>G

Benign

BA1 BS2_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

The c.878A>G (NM_000536.4) variant in RAG2 is a missense variant predicted to cause the substitution of Glutamic Acid by Glycine at amino acid 293 (p.Glu293Gly). The filtering allele frequency (the lower threshold of the 95% CI of 7999/75012 alleles) of the c.878A>G variant in RAG2 is 0.1047 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1, and therefore meets this criterion (BA1). Additionally, 437 adult homozygous occurrences are reported in gnomAD v4 (BS2_Supporting) In summary, this variant meets the criteria to be classified as Benign for autosomal recessive recombinase activating gene 2 deficiency based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1)

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 7999/75012 alleles) of the c.878A>G variant in RAG2 is 0.1047 for African/African American chromosomes by gnomAD v4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1, and therefore meets this criterion (BA1).

BS2_Supporting

Additionally, 437 adult homozygous occurrences are reported in gnomAD v4 (BS2_Supporting)

Curation History

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