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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:
RCV001800841.7

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002045356Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Nov 7, 2021) 		germlineclinical testing

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

SCV002238865Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Oct 19, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

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

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From Invitae, SCV002238865.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical 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).

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

Last Updated: Sep 1, 2024