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NM_002485.5(NBN):c.1750G>T (p.Glu584Ter) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Dec 8, 2021
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:
RCV000636737.5

Allele description [Variation Report for NM_002485.5(NBN):c.1750G>T (p.Glu584Ter)]

NM_002485.5(NBN):c.1750G>T (p.Glu584Ter)

Gene:
NBN:nibrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_002485.5(NBN):c.1750G>T (p.Glu584Ter)
HGVS:
  • NC_000008.11:g.89953339C>A
  • NG_008860.1:g.36333G>T
  • NM_001024688.3:c.1504G>T
  • NM_002485.5:c.1750G>TMANE SELECT
  • NP_001019859.1:p.Glu502Ter
  • NP_002476.2:p.Glu584Ter
  • NP_002476.2:p.Glu584Ter
  • LRG_158t1:c.1750G>T
  • LRG_158:g.36333G>T
  • LRG_158p1:p.Glu584Ter
  • NC_000008.10:g.90965567C>A
  • NM_002485.4:c.1750G>T
Protein change:
E502*
Links:
dbSNP: rs1554558270
NCBI 1000 Genomes Browser:
rs1554558270
Molecular consequence:
  • NM_001024688.3:c.1504G>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_002485.5:c.1750G>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Microcephaly, normal intelligence and immunodeficiency (NBS)
Synonyms:
IMMUNODEFICIENCY, MICROCEPHALY, AND CHROMOSOMAL INSTABILITY; SEEMANOVA SYNDROME II; Nijmegen breakage syndrome; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0009623; MedGen: C0398791; Orphanet: 647; OMIM: 251260

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000758177Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Dec 8, 2021)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Nibrin, a novel DNA double-strand break repair protein, is mutated in Nijmegen breakage syndrome.

Varon R, Vissinga C, Platzer M, Cerosaletti KM, Chrzanowska KH, Saar K, Beckmann G, Seemanová E, Cooper PR, Nowak NJ, Stumm M, Weemaes CM, Gatti RA, Wilson RK, Digweed M, Rosenthal A, Sperling K, Concannon P, Reis A.

Cell. 1998 May 1;93(3):467-76.

PubMed [citation]
PMID:
9590180

Mild Nijmegen breakage syndrome phenotype due to alternative splicing.

Varon R, Dutrannoy V, Weikert G, Tanzarella C, Antoccia A, Stöckl L, Spadoni E, Krüger LA, di Masi A, Sperling K, Digweed M, Maraschio P.

Hum Mol Genet. 2006 Mar 1;15(5):679-89. Epub 2006 Jan 13.

PubMed [citation]
PMID:
16415040
See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000758177.4

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

ClinVar contains an entry for this variant (Variation ID: 530738). For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Glu584*) in the NBN gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in NBN are known to be pathogenic (PMID: 9590180, 16415040).

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

Last Updated: Sep 29, 2024