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_000536.4(RAG2):c.1158C>A (p.Phe386Leu)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA293061

138887 (ClinVar)

Gene: RAG2

Condition: recombinase activating gene 2 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 85a75daf-5427-494d-a55d-98c8fa7e91d5

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000536.4:c.1158C>A

NM_000536.4(RAG2):c.1158C>A (p.Phe386Leu)

NC_000011.10:g.36593011G>T

CM000673.2:g.36593011G>T

NC_000011.9:g.36614561G>T

CM000673.1:g.36614561G>T

NC_000011.8:g.36571137G>T

NG_007573.1:g.10226C>A

NG_033154.1:g.3519G>T

ENST00000311485.8:c.1158C>A

ENST00000311485.7:c.1158C>A

ENST00000524423.1:n.131+5091C>A

ENST00000534663.1:c.*130G>T

ENST00000618712.4:c.1158C>A

NM_000536.3:c.1158C>A

NM_001243785.1:c.1158C>A

NM_001243786.1:c.1158C>A

NM_001243785.2:c.1158C>A

NM_001243786.2:c.1158C>A

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 NM_000536.4:c.1158C>A variant in RAG2 is a missense variant predicted to cause substitution of phenylalanine by leucine at amino acid 386 (p.Phe386Leu). This variant has a population max filtering allele frequency of 0.01649 in the European (non-Finnish) population in gnomAD, which is above the threshold for BA1 set by the ClinGen SCID VCEP for RAG2 (>0.00872). In addition, this variant is present in 23 homozygotes in gnomAD (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG criteria applied: BA1 and BS2_Supporting as specified by the ClinGen SCID VCEP (VCEP specifications version 1).

BA1

The overall MAF of this variant in gnomAD is 0.00975 (2756/282728 alleles) and in the European (non-Finnish) population the MAF is 0.01649 (2129/129084 alleles). These frequencies are higher than the cutoff set for BA1 by the ClinGen SCID VCEP for RAG2 (>0.00872). Therefore, BA1 is met. Also there are 23 homozygotes in gnomAD.

BS2_Supporting

23 homozygotes in gnomAD, Bs2_Supporting.

Curation History

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