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NM_000448.3(RAG1):c.2882_2891del (p.Ser961fs) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jul 14, 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:
RCV002004080.7

Allele description [Variation Report for NM_000448.3(RAG1):c.2882_2891del (p.Ser961fs)]

NM_000448.3(RAG1):c.2882_2891del (p.Ser961fs)

Gene:
RAG1:recombination activating 1 [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
11p12
Genomic location:
Preferred name:
NM_000448.3(RAG1):c.2882_2891del (p.Ser961fs)
HGVS:
  • NC_000011.10:g.36576186_36576195del
  • NG_007528.1:g.13174_13183del
  • NM_000448.3:c.2882_2891delMANE SELECT
  • NM_001377277.1:c.2882_2891del
  • NM_001377278.1:c.2882_2891del
  • NM_001377279.1:c.2882_2891del
  • NM_001377280.1:c.2882_2891del
  • NP_000439.2:p.Ser961fs
  • NP_001364206.1:p.Ser961fs
  • NP_001364207.1:p.Ser961fs
  • NP_001364208.1:p.Ser961fs
  • NP_001364209.1:p.Ser961fs
  • LRG_98:g.13174_13183del
  • NC_000011.9:g.36597734_36597743del
  • NC_000011.9:g.36597736_36597745del
Protein change:
S961fs
Links:
dbSNP: rs1195475275
NCBI 1000 Genomes Browser:
rs1195475275
Molecular consequence:
  • NM_000448.3:c.2882_2891del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377277.1:c.2882_2891del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377278.1:c.2882_2891del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377279.1:c.2882_2891del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_001377280.1:c.2882_2891del - 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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002288245Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Jul 14, 2023) 		germlineclinical testing

PubMed (4)
[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

Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome.

Corneo B, Moshous D, Güngör T, Wulffraat N, Philippet P, Le Deist FL, Fischer A, de Villartay JP.

Blood. 2001 May 1;97(9):2772-6.

PubMed [citation]
PMID:
11313270

Clinical application of DNA microarrays: molecular diagnosis and HLA matching of an Amish child with severe combined immune deficiency.

Strauss KA, Puffenberger EG, Bunin N, Rider NL, Morton MC, Eastman JT 3rd, Morton DH.

Clin Immunol. 2008 Jul;128(1):31-8. doi: 10.1016/j.clim.2008.02.016. Epub 2008 Apr 28.

PubMed [citation]
PMID:
18442948
See all PubMed Citations (4)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002288245.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (4)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the RAG1 protein in which other variant(s) (p.Lys992Glu) have been determined to be pathogenic (PMID: 11313270, 18442948, 24290284). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 1505484). This variant has not been reported in the literature in individuals affected with RAG1-related conditions. This variant is present in population databases (no rsID available, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ser961Metfs*14) in the RAG1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 83 amino acid(s) of the RAG1 protein.

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

Last Updated: Apr 7, 2025