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NM_000448.3(RAG1):c.2410del (p.Ala804fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 19, 2023
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV003782587.2

Allele description [Variation Report for NM_000448.3(RAG1):c.2410del (p.Ala804fs)]

NM_000448.3(RAG1):c.2410del (p.Ala804fs)

Gene:
RAG1:recombination activating 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11p12
Genomic location:
Preferred name:
NM_000448.3(RAG1):c.2410del (p.Ala804fs)
HGVS:
  • NC_000011.10:g.36575714del
  • NG_007528.1:g.12702del
  • NM_000448.3:c.2410delMANE SELECT
  • NM_001377277.1:c.2410del
  • NM_001377278.1:c.2410del
  • NM_001377279.1:c.2410del
  • NM_001377280.1:c.2410del
  • NP_000439.1:p.Ala804Glnfs
  • NP_000439.2:p.Ala804fs
  • NP_001364206.1:p.Ala804fs
  • NP_001364207.1:p.Ala804fs
  • NP_001364208.1:p.Ala804fs
  • NP_001364209.1:p.Ala804fs
  • LRG_98t1:c.2410del
  • LRG_98:g.12702del
  • LRG_98p1:p.Ala804Glnfs
  • NC_000011.9:g.36597264del
  • NM_000448.2:c.2410delG
Protein change:
A804fs
Molecular consequence:
  • NM_000448.3:c.2410del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377277.1:c.2410del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377278.1:c.2410del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377279.1:c.2410del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377280.1:c.2410del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
Combined immunodeficiency with skin granulomas
Synonyms:
Combined cellular and humoral immune defects with granulomas
Identifiers:
MONDO: MONDO:0009306; MedGen: C2673536; OMIM: 233650
Name:
Severe combined immunodeficiency, autosomal recessive, T cell-negative, B cell-negative, NK cell-positive
Synonyms:
SCID, T CELL-NEGATIVE, B CELL-NEGATIVE, NK CELL-POSITIVE; Severe immunodeficiency, autosomal recessive, T-cell negative, B-cell negative, NK cell-positive; SCID, AR, T-cell negative, B-cell negative, NK cell-positive; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0011086; MedGen: C1832322; Orphanet: 331206; OMIM: 601457

Recent activity

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004604045Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Dec 19, 2023) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Vasculitis as a Major Morbidity Factor in Patients With Partial RAG Deficiency.

Geier CB, Farmer JR, Foldvari Z, Ujhazi B, Steininger J, Sleasman JW, Parikh S, Dilley MA, Pai SY, Henderson L, Hazen M, Neven B, Moshous D, Sharapova SO, Mihailova S, Yankova P, Naumova E, Özen S, Byram K, Fernandez J, Wolf HM, Eibl MM, et al.

Front Immunol. 2020;11:574738. doi: 10.3389/fimmu.2020.574738.

PubMed [citation]
PMID:
33193364
PMCID:
PMC7609967

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004604045.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Ala804Glnfs*10) in the RAG1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 240 amino acid(s) of the RAG1 protein. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. This variant disrupts a region of the RAG1 protein in which other variant(s) (p.His994Arg) have been determined to be pathogenic (PMID: 33193364; Invitae). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Sep 29, 2024