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.35T>C (p.Ile12Thr)

CA5950633

573475 (ClinVar)

Gene: RAG2

Condition: recombinase activating gene 2 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: ed04ab15-ccd2-4f7e-b32a-40003882b24f

Approved on: 2024-06-10

Published on: 2024-06-10

HGVS expressions

NM_000536.4:c.35T>C

NM_000536.4(RAG2):c.35T>C (p.Ile12Thr)

NC_000011.10:g.36594134A>G

CM000673.2:g.36594134A>G

NC_000011.9:g.36615684A>G

CM000673.1:g.36615684A>G

NC_000011.8:g.36572260A>G

NG_007573.1:g.9103T>C

NG_033154.1:g.4642A>G

ENST00000527033.6:c.35T>C

ENST00000529083.2:c.35T>C

ENST00000532616.2:c.35T>C

ENST00000311485.8:c.35T>C

ENST00000311485.7:c.35T>C

ENST00000524423.1:n.131+3968T>C

ENST00000527033.5:c.35T>C

ENST00000529083.1:c.35T>C

ENST00000618712.4:c.35T>C

NM_000536.3:c.35T>C

NM_001243785.1:c.35T>C

NM_001243786.1:c.35T>C

NM_001243785.2:c.35T>C

NM_001243786.2:c.35T>C

Uncertain Significance

PM1_Supporting

PM2

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

NM_000536.4(RAG2):c.35T>C is a missense variant predicted to cause substitution of Isoleucine by Threonine at amino acid 12 (p.Ile12Thr).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 0.001750 (151/75030) in African/African American population. (PM2_Supporting, BS1 and BA1 are not met). 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 (VCEP specifications version 1).

PM1_Supporting

This missense variant is located in the core domain (amino acids 1-383) (PM1_supporting).

PM2

The highest population minor allele frequency in gnomAD v4 is 0.001750 (151/75030) in African/African American population. (PM2_Supporting, BS1 and BA1 are not met)

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