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.2751G>A (p.Gln917=)

CA5950313

304506 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: e9f7086e-9047-42aa-bcaa-d49a28b3dca9

Approved on: 2024-01-23

Published on: 2024-01-23

HGVS expressions

NM_000448.3:c.2751G>A

NM_000448.3(RAG1):c.2751G>A (p.Gln917=)

NC_000011.10:g.36576055G>A

CM000673.2:g.36576055G>A

NC_000011.9:g.36597605G>A

CM000673.1:g.36597605G>A

NC_000011.8:g.36554181G>A

NG_007528.1:g.13043G>A

ENST00000299440.6:c.2751G>A

ENST00000299440.5:c.2751G>A

ENST00000524423.1:n.132-84C>T

ENST00000534663.1:c.2751G>A

NM_000448.2:c.2751G>A

NM_001377277.1:c.2751G>A

NM_001377278.1:c.2751G>A

NM_001377279.1:c.2751G>A

NM_001377280.1:c.2751G>A

Likely Benign

BP7 BS1

BS2

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.2751G>A (p.Gln917=) variant (NM_000448.3) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7). The highest population minor allele frequency in gnomAD v2.1.1 is 0.007464 (220/24818 alleles) in African/African American population, which is higher than the ClinGen SCID VCEP threshold (>0.00195) for BS1, and therefore meets this criterion (BS1). No homozygous has been reported. (BS2 not met). In summary, this variant is classified as a Likely Benign for autosomal recessive SCID based on ACMG/AMP criteria applied, as specified by the ClinGen SCID VCEP (specification version 1.0): BS1 and BP7.

BP7

The c.2751G>A (p.Gln917=) variant (NM_000448.3) is a synonymous (silent) variant that is not predicted by SpliceAI and varSEAK to impact splicing (BP7).

BS1

The highest population minor allele frequency in gnomAD v2.1.1 is 0.007464 (220/24818 alleles) in African/African American population, which is higher than the ClinGen SCID VCEP threshold (>0.00195) for BS1, and therefore meets this criterion (BS1).

BS2

No homozygous has been reported.

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