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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000758177	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Dec 8, 2021)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 9590180, 16415040, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000758177

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Dec 8, 2021)

germline

clinical testing

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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).

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

Last Updated: Sep 29, 2024

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