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.2638G>A (p.Glu880Lys)

CA293052

138884 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: 02968afa-1298-4a0c-aea4-61ca4fa8fc1a

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_000448.3:c.2638G>A

NM_000448.3(RAG1):c.2638G>A (p.Glu880Lys)

NC_000011.10:g.36575942G>A

CM000673.2:g.36575942G>A

NC_000011.9:g.36597492G>A

CM000673.1:g.36597492G>A

NC_000011.8:g.36554068G>A

NG_007528.1:g.12930G>A

ENST00000299440.6:c.2638G>A

ENST00000299440.5:c.2638G>A

ENST00000524423.1:n.161C>T

ENST00000534663.1:c.2638G>A

NM_000448.2:c.2638G>A

NM_001377277.1:c.2638G>A

NM_001377278.1:c.2638G>A

NM_001377279.1:c.2638G>A

NM_001377280.1:c.2638G>A

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.2638G>A variant in RAG1 is a missense variant predicted to cause the substitution of Glutamic Acid by Lysine at amino acid 880 (p.Glu880Lys). The filtering allele frequency (the lower threshold of the 95% CI of 3496/75044) of the c.2638G>A variant in RAG1 is 0.04730 for African/African American 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, 84 homozygous adults are reported on gnomAD v.4 (BS2_Supporting). In summary, this variant meets the criteria to be classified as Benign for autosomal recessive SCID based on the ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: BA1 and BS2_Supporting. (VCEP specifications version 1).

BS2_Supporting

84 homozygous adults are reported on GnomAD v.4, BS2_Supporting is Met.

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 3496/75044) of the c.2638G>A variant in RAG1 is 0.04730 for African/African American chromosomes by gnomAD v.4, which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1, and therefore meets this criterion (BA1).

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