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]

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Variant: NM_000536.4(RAG2):c.644C>T (p.Thr215Ile)

CA122864

13135 (ClinVar)

Gene: RAG2

Condition: recombinase activating gene 2 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 76b80f29-618c-4760-a6d1-807615561d42

HGVS expressions

NM_000536.4:c.644C>T

NM_000536.4(RAG2):c.644C>T (p.Thr215Ile)

NC_000011.10:g.36593525G>A

CM000673.2:g.36593525G>A

NC_000011.9:g.36615075G>A

CM000673.1:g.36615075G>A

NC_000011.8:g.36571651G>A

NG_007573.1:g.9712C>T

NG_033154.1:g.4033G>A

ENST00000311485.8:c.644C>T

ENST00000311485.7:c.644C>T

ENST00000524423.1:n.131+4577C>T

ENST00000618712.4:c.644C>T

NM_000536.3:c.644C>T

NM_001243785.1:c.644C>T

NM_001243786.1:c.644C>T

NM_001243785.2:c.644C>T

NM_001243786.2:c.644C>T

Benign

BS2_Supporting BA1

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.644C>T (NM_000536.4) variant in RAG2 is a missense variant predicted to cause substitution of Threonine by Isoleucine at amino acid 215 (p.Thr215Ile). The filtering allele frequency (the lower threshold of the 95% CI of 2177/91084 alleles) of the c.644C>T variant in RAG2 is 0.02308 for South Asian chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1, and therefore meets this criterion (BA1). Additionally, 42 homozygous individuals have been described (40 and 2 individuals in South Asian and "Remaining" populations, respectively (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. Criteria applied: BA1 and BS2_Supporting (VCEP specifications version 1.0).

BS2_Supporting

42 homozygous individuals have been described in gnomAD v.4 (BS2_Supporting).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 2177/91084 alleles) of the c.644C>T variant in RAG2 is 0.02308 for South Asian chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1, and therefore meets this criterion (BA1). Additionally, 42 homozygous individuals have been described.

Approved on: 2024-01-23

Published on: 2024-01-23

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