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NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp) AND Recombinase activating gene 1 deficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Feb 26, 2024
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003991473.1

Allele description [Variation Report for NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)]

NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)

Gene:
RAG1:recombination activating 1 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
11p12
Genomic location:
Preferred name:
NM_000448.3(RAG1):c.2442G>T (p.Glu814Asp)
Other names:
NM_000448.3(RAG1):c.2442G>T; p.Glu814Asp
HGVS:
  • NC_000011.10:g.36575746G>T
  • NG_007528.1:g.12734G>T
  • NM_000448.3:c.2442G>TMANE SELECT
  • NM_001377277.1:c.2442G>T
  • NM_001377278.1:c.2442G>T
  • NM_001377279.1:c.2442G>T
  • NM_001377280.1:c.2442G>T
  • NP_000439.1:p.Glu814Asp
  • NP_000439.2:p.Glu814Asp
  • NP_001364206.1:p.Glu814Asp
  • NP_001364207.1:p.Glu814Asp
  • NP_001364208.1:p.Glu814Asp
  • NP_001364209.1:p.Glu814Asp
  • LRG_98t1:c.2442G>T
  • LRG_98:g.12734G>T
  • LRG_98p1:p.Glu814Asp
  • NC_000011.9:g.36597296G>T
  • NM_000448.2:c.2442G>T
Protein change:
E814D
Links:
dbSNP: rs768860215
NCBI 1000 Genomes Browser:
rs768860215
Molecular consequence:
  • NM_000448.3:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377277.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377278.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377279.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001377280.1:c.2442G>T - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Recombinase activating gene 1 deficiency
Identifiers:
MONDO: MONDO:0000572; MedGen: CN375631

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004809116ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen
reviewed by expert panel

(ClinGen SCID ACMG Specifications RAG1 V1.0.0)		Uncertain significance
(Feb 26, 2024) 		germlinecuration

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Severe Combined Immunodeficiency Variant Curation Expert Panel, ClinGen, SCV004809116.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

NM_000448.3(RAG1):c.2442G>T is a missense variant predicted to cause substitution of Glutamic Acid by Aspartic Acid at amino acid 814 (p.Glu814Asp). This missense variant is located in the core domain (amino acids 387-1011) (PM1_Supporting). The filtering allele frequency (the upper threshold of the 95% CI of 3/44724) of the c.2442G>T variant in RAG1 is 0.00001779 for Admixed American chromosomes by gnomAD v4, which is lower than the ClinGen SCID VCEP threshold (<0.000102) for PM2_Supporting, and therefore meets this criterion (PM2_Supporting). 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,PM2_Supporting(VCEP specifications version 1).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 29, 2024