Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computer assertion could be determined for this classification!

Variant: NM_000448.3(RAG1):c.40G>A (p.Ala14Thr)

CA5949893

1348464 (ClinVar)

Gene: RAG1
Condition: recombinase activating gene 1 deficiency
Inheritance Mode: Autosomal recessive inheritance
Link to MONDO
UUID: a199dfdd-d6b1-4ce7-9be8-6e1c2c4ec103
Approved on: 2024-04-23
Published on: 2024-04-23

HGVS expressions

NM_000448.3:c.40G>A
NM_000448.3(RAG1):c.40G>A (p.Ala14Thr)
NC_000011.10:g.36573344G>A
CM000673.2:g.36573344G>A
NC_000011.9:g.36594894G>A
CM000673.1:g.36594894G>A
NC_000011.8:g.36551470G>A
NG_007528.1:g.10332G>A
ENST00000697713.1:c.40G>A
ENST00000697714.1:c.40G>A
ENST00000697715.1:c.40G>A
ENST00000299440.6:c.40G>A
ENST00000299440.5:c.40G>A
ENST00000534663.1:c.40G>A
NM_000448.2:c.40G>A
NM_001377277.1:c.40G>A
NM_001377278.1:c.40G>A
NM_001377279.1:c.40G>A
NM_001377280.1:c.40G>A
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Uncertain Significance

Met criteria codes 1
PM2_Supporting
Not Met criteria codes 1
PS3

Evidence Links 0

Expert Panel

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.40G>A variant in RAG1 is a missense variant predicted to cause a substitution of alanine by threonine at amino acid 14 (p.Ala14Thr). The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008797 (1/113676 alleles) in the European (non-Finnish) population, which is lower than the SCID-VCEP threshold (<0.000102) for PM2_Supporting. No homozygous individual has been observed in the gnomAD v2.1.1(PM2_Supporting). This variant has not been reported in the literature in individuals with SCID. In ClinVar, the variant was reported in one affected individual who didn't have a second RAG1 variant, and the variant was classified as a Variant of Uncertain Significance (Invitae, SCV002113580.2). There is no functional evidence for this variant. Due to insufficient evidence, this variant is classified as a variant of uncertain significance for SCID. ACMG/AMP criteria applied, as specified by the ClinGen SCID-VCEP: PM2_supporting (SCID VCEP specifications version 1.0).
Met criteria codes
PM2_Supporting
The highest population minor allele frequency in gnomAD v2.1.1 is 0.000008797 (1/113676 alleles) in the European (non-Finnish) population, which is lower than the SCID-VCEP threshold (<0.000102) for PM2_Supporting. No homozygous individual has been observed in the gnomAD v2.1.1. (PM2_Supporting)
Not Met criteria codes
PS3
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
Curation History
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