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NM_002485.5(NBN):c.657_661del (p.Lys219fs) AND NBN-related disorder

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 20, 2024
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:
RCV003389666.5

Allele description [Variation Report for NM_002485.5(NBN):c.657_661del (p.Lys219fs)]

NM_002485.5(NBN):c.657_661del (p.Lys219fs)

Gene:
NBN:nibrin [Gene - OMIM - HGNC]
Variant type:
Deletion
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_002485.5(NBN):c.657_661del (p.Lys219fs)
Other names:
657del5
HGVS:
  • NC_000008.10:g.90983445_90983449delGTTTT
  • NC_000008.11:g.89971217_89971221del
  • NG_008860.1:g.18454_18458del
  • NM_001024688.3:c.411_415del
  • NM_002485.5:c.657_661delMANE SELECT
  • NP_001019859.1:p.Lys137fs
  • NP_002476.2:p.Lys219fs
  • LRG_158:g.18454_18458del
  • NC_000008.10:g.90983442_90983446del
  • NC_000008.10:g.90983442_90983446delTTTGT
  • NC_000008.10:g.90983445_90983449del
  • NC_000008.10:g.90983445_90983449del
  • NC_000008.10:g.90983445_90983449delGTTTT
  • NM_002485.4:c.657_661delACAAA
  • NM_002485.5:c.657_661delACAAAMANE SELECT
  • NP_002476.2:p.Lys219AsnfsTer15
  • p.K219NFS*16
  • p.K219NfsX16
  • p.Lys219AsnfsX16
Protein change:
K137fs
Links:
OMIM: 602667.0001; dbSNP: rs587776650
NCBI 1000 Genomes Browser:
rs587776650
Molecular consequence:
  • NM_001024688.3:c.411_415del - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_002485.5:c.657_661del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:
NBN-related disorder
Synonyms:
NBN-related condition
Identifiers:

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000806448PreventionGenetics, part of Exact Sciences
no assertion criteria provided
Pathogenic
(Jun 20, 2024) 		germlineclinical testing

Help

Summary from all submissions

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000806448.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The NBN c.657_661del5 variant is predicted to result in a frameshift and premature protein termination (p.Lys219Asnfs*16). The c.657_661del variant (also known as c.657del5) in the NBN gene is a founder pathogenic variant in the Slavic population and causes Nijmegen breakage syndrome in the homozygous state or in combination with another pathogenic variant in NBN (Varon et al. 1998. PubMed ID: 9590180). Functionally, it has been hypothesized to be a hypomorph, which results in a truncated protein with residual activity of the full-length NBN protein (Maser et al. 2001. PubMed ID: 11279524; Dzikiewicz-Krawczyk et al. 2011. PubMed ID: 22131123). However, this variant is reported in 0.040% of alleles in individuals of European (Non-Finnish) descent in gnomAD. In ClinVar, this variant has been classified as pathogenic as well as a risk factor (https://www.ncbi.nlm.nih.gov/clinvar/variation/6940/). Frameshift variants in NBN are expected to be pathogenic. This variant is interpreted as pathogenic.

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

Last Updated: Nov 3, 2024