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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000448.3(RAG1):c.2603C>T (p.Ala868Val)

CA214197

36712 (ClinVar)

Gene: RAG1

Condition: recombinase activating gene 1 deficiency

Inheritance Mode: Autosomal recessive inheritance

Link to MONDO

UUID: b0cfbcae-2fa6-45af-872f-83882246dd3f

HGVS expressions

NM_000448.3:c.2603C>T

NM_000448.3(RAG1):c.2603C>T (p.Ala868Val)

NC_000011.10:g.36575907C>T

CM000673.2:g.36575907C>T

NC_000011.9:g.36597457C>T

CM000673.1:g.36597457C>T

NC_000011.8:g.36554033C>T

NG_007528.1:g.12895C>T

ENST00000299440.6:c.2603C>T

ENST00000299440.5:c.2603C>T

ENST00000524423.1:n.196G>A

ENST00000534663.1:c.2603C>T

NM_000448.2:c.2603C>T

NM_001377277.1:c.2603C>T

NM_001377278.1:c.2603C>T

NM_001377279.1:c.2603C>T

NM_001377280.1:c.2603C>T

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 RAG1 Version 1.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Severe Combined Immunodeficiency Disease VCEP

NM_000448.3(RAG1):c.2603C>T is a missense variant predicted to cause substitution of Alanine by Valine at amino acid 868 (p.Ala868Val). This missense variant is located in the core domain (amino acids 387-1011) (PM1_Supporting). The highest population minor allele frequency in gnomAD v4 is 0.0001585 (187/1180040) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). There are no publications for this variant in the literature. In summary, this variant meets the criteria to be classified as a variant of uncertain significance for autosomal recessive severe combined immunodeficiency due to RAG1 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 387-1011) (PM1_Supporting).

PM2

The highest population minor allele frequency in gnomAD v4 is 0.0001585 (187/1180040) in European (non-Finnish) population. (PM2_Supporting, BS1, and BA1 are not met)

Approved on: 2024-02-12

Published on: 2024-02-12

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