NM_002485.5(NBN):c.800dup (p.Thr268fs) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:: Pathogenic (2 submissions)
Last evaluated:: Nov 7, 2021
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV001800841.8

Allele description [Variation Report for NM_002485.5(NBN):c.800dup (p.Thr268fs)]

NM_002485.5(NBN):c.800dup (p.Thr268fs)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

Duplication

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.800dup (p.Thr268fs)

HGVS:

NC_000008.11:g.89970462dup
NG_008860.1:g.19212dup
NM_001024688.3:c.554dup
NM_002485.5:c.800dupMANE SELECT
NP_001019859.1:p.Thr186fs
NP_002476.2:p.Thr268fs
NP_002476.2:p.Thr268fs
LRG_158t1:c.800dup
LRG_158:g.19212dup
LRG_158p1:p.Thr268fs
NC_000008.10:g.90982687_90982688insC
NC_000008.10:g.90982690dup
NM_002485.4:c.800dup
NM_002485.4:c.800dupG

Protein change:

T186fs

Links:

dbSNP: rs1554563955

NCBI 1000 Genomes Browser:

rs1554563955

Molecular consequence:

NM_001024688.3:c.554dup - frameshift variant - [Sequence Ontology: SO:0001589]
NM_002485.5:c.800dup - frameshift variant - [Sequence Ontology: SO:0001589]

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

Recent activity

Clear Turn Off Turn On

Helicobacter pylori strain MHP51 accn210.5591.4445_324_cov_10.520451210.5591, wh...
Helicobacter pylori strain MHP51 accn210.5591.4445_324_cov_10.520451210.5591, whole genome shotgun sequence
gi|1783736607|ref|NZ_WACV01000044.1 |WGS:NZ_WACV01|accn210.5591.4445_324_cov_10.520451210.5591

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002045356	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Pathogenic (Nov 7, 2021)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002238865	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Oct 19, 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

SCV002045356

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Pathogenic
(Nov 7, 2021)

germline

clinical testing

PubMed (1)
[See all records that cite this PMID]

SCV002238865

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Oct 19, 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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

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

See all PubMed Citations (4)

Details of each submission

From Genome-Nilou Lab, SCV002045356.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (1)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002238865.3

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

Description

For these reasons, this variant has been classified as Pathogenic. This variant has not been reported in the literature in individuals with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 545860). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Thr268Asnfs*5) 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: Nov 3, 2024

ClinVar

Relating variation to medicine