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_000448.3(RAG1):c.303G>A (p.Ala101=)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA293046

138882 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: d3b4ef76-02a8-4269-9cfa-7e8c9ddd34a5

Approved on: 2024-01-17

Published on: 2024-01-17

HGVS expressions

NM_000448.3:c.303G>A

NM_000448.3(RAG1):c.303G>A (p.Ala101=)

NC_000011.10:g.36573607G>A

CM000673.2:g.36573607G>A

NC_000011.9:g.36595157G>A

CM000673.1:g.36595157G>A

NC_000011.8:g.36551733G>A

NG_007528.1:g.10595G>A

ENST00000299440.6:c.303G>A

ENST00000299440.5:c.303G>A

ENST00000534663.1:c.303G>A

NM_000448.2:c.303G>A

NM_001377277.1:c.303G>A

NM_001377278.1:c.303G>A

NM_001377279.1:c.303G>A

NM_001377280.1:c.303G>A

Benign

BS2_Supporting BA1 BP7

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 c.303G>A (p.Ala101=) variant (NM_000022.4) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7). The filtering allele frequency (the lower threshold of the 95% CI of 799/30614) of the c.303G>A variant in RAG1 is 0.02460 for South Asian chromosomes by gnomAD v2.1.1 which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1 and therefore meets this criterion (BA1). Additionally, 76 homozygous individuals were reported (BS2_Supporting is met). In summary, this variant is classified as a Benign for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): BA1, BS2_Supporting, and BP7.

BS2_Supporting

There are 76 homozygous individuals reported (gnomAD v.2.1.1).

BA1

The filtering allele frequency (the lower threshold of the 95% CI of 799/30614) of the c.303G>A variant in RAG1 is 0.02460 for South Asian chromosomes by gnomAD v2.1.1 which is higher than the ClinGen SCID VCEP threshold (>0.00872) for BA1 and therefore meets this criterion (BA1). Additionally, 76 homozygous individuals were reported.

BP7

The c.303G>A (p.Ala101=) variant (NM_000022.4) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.