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_000448.3(RAG1):c.251A>G (p.His84Arg)

CA5949933

378467 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 3b035dd6-9008-48f6-993a-b85715aecd8c

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_000448.3:c.251A>G

NM_000448.3(RAG1):c.251A>G (p.His84Arg)

NC_000011.10:g.36573555A>G

CM000673.2:g.36573555A>G

NC_000011.9:g.36595105A>G

CM000673.1:g.36595105A>G

NC_000011.8:g.36551681A>G

NG_007528.1:g.10543A>G

ENST00000299440.6:c.251A>G

ENST00000299440.5:c.251A>G

ENST00000534663.1:c.251A>G

NM_000448.2:c.251A>G

NM_001377277.1:c.251A>G

NM_001377278.1:c.251A>G

NM_001377279.1:c.251A>G

NM_001377280.1:c.251A>G

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 RAG1 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_000448.3:c.251A>G variant in RAG1 is a missense variant predicted to cause the substitution of Histidine by Arginine at amino acid 249 (p.His84Arg). The Popmax Filtering allele frequency (95% CI) of the c.251A>G variant in RAG1 is 0.01622 in gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1. Therefore, BA1 is met. Additionally, 19 homozygous adults are reported on GnomAD v.4, BS2_Supporting is Met. In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1).

BS2_Supporting

19 homozygous adults are reported on GnomAD v2.1.1, BS2_Supporting is Met.

BA1

The Popmax Filtering allele frequency (95% CI) of the c.251A>G variant in RAG1 is 0.01622 in gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1. Therefore, BA1 is met.

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