NM_000448.3(RAG1):c.256_257del (p.Lys86fs) AND Histiocytic medullary reticulosis

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 1, 2005
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV002279719.1

Allele description [Variation Report for NM_000448.3(RAG1):c.256_257del (p.Lys86fs)]

NM_000448.3(RAG1):c.256_257del (p.Lys86fs)

Gene:

RAG1:recombination activating 1 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

11p12

Genomic location:

Preferred name:

NM_000448.3(RAG1):c.256_257del (p.Lys86fs)

Other names:

NM_000448.3(RAG1):c.256_257del; p.Lys86fs

HGVS:

NC_000011.10:g.36573560_36573561del
NG_007528.1:g.10548_10549del
NM_000448.3:c.256_257delMANE SELECT
NM_001377277.1:c.256_257del
NM_001377278.1:c.256_257del
NM_001377279.1:c.256_257del
NM_001377280.1:c.256_257del
NP_000439.2:p.Lys86fs
NP_001364206.1:p.Lys86fs
NP_001364207.1:p.Lys86fs
NP_001364208.1:p.Lys86fs
NP_001364209.1:p.Lys86fs
LRG_98:g.10548_10549del
NC_000011.9:g.36595110_36595111del
NM_000448.2:c.256_257delAA
NM_000448.3:c.256_257del

Links:

OMIM: 179615.0013; dbSNP: rs772962160

NCBI 1000 Genomes Browser:

rs772962160

Molecular consequence:

NM_000448.3:c.256_257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001377277.1:c.256_257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001377278.1:c.256_257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001377279.1:c.256_257del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001377280.1:c.256_257del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Histiocytic medullary reticulosis
Synonyms:: Omenn syndrome; Reticuloendotheliosis familial with eosinophilia; Severe combined immunodeficiency with hypereosinophilia
Identifiers:: MONDO: MONDO:0011338; MedGen: C2700553; Orphanet: 39041; OMIM: 603554

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000034281	OMIM	no assertion criteria provided	Pathogenic (Nov 1, 2005)	germline	literature only	PubMed (3) [See all records that cite these PMIDs] 9630231, 11121059, 16276422

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000034281

OMIM

no assertion criteria provided

Pathogenic
(Nov 1, 2005)

germline

literature only

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Partial V(D)J recombination activity leads to Omenn syndrome.

Villa A, Santagata S, Bozzi F, Giliani S, Frattini A, Imberti L, Gatta LB, Ochs HD, Schwarz K, Notarangelo LD, Vezzoni P, Spanopoulou E.

Cell. 1998 May 29;93(5):885-96.

PubMed [citation]

PMID:: 9630231

N-terminal RAG1 frameshift mutations in Omenn's syndrome: internal methionine usage leads to partial V(D)J recombination activity and reveals a fundamental role in vivo for the N-terminal domains.

Santagata S, Gomez CA, Sobacchi C, Bozzi F, Abinun M, Pasic S, Cortes P, Vezzoni P, Villa A.

Proc Natl Acad Sci U S A. 2000 Dec 19;97(26):14572-7.

PubMed [citation]

PMID:: 11121059
PMCID:: PMC18960

See all PubMed Citations (3)

Details of each submission

From OMIM, SCV000034281.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (3)

Description

Villa et al. (1998) found a deletion of 2 nucleotides of RAG1 cDNA in heterozygous state in a patient with Omenn syndrome (603554). This mutation results in a truncated protein.

Santagata et al. (2000) demonstrated that a 2-bp deletion (AA) at nucleotides 368 and 369 results in a frameshift at proline-85 and addition of 32 amino acids before a stop. In 1 patient the deletion was combined in compound heterozygous state with the D429G missense mutation (179615.0009); in another patient it was combined with the E722K (179615.0001) missense mutation. In yet another patient the 2-bp deletion was present in homozygous state.

De Villartay et al. (2005) identified the RAG1 368AA deletion in homozygous state in a Turkish child of consanguineous parents who presented with severe, persistent cytomegalovirus infection, anti-red blood cell antibody-induced anemia, a high percentage of gamma/delta T cells, and a low percentage of alpha/beta T cells (609889).

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Oct 8, 2024

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