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:

Recent activity

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hemoglobin 4 [Lethenteron camtschaticum]
hemoglobin 4 [Lethenteron camtschaticum]
gi|126143347|dbj|BAF47286.1|

Protein
Gelidium divaricatum voucher CNU019163 cytochrome c oxidase subunit I (cox1) gen...
Gelidium divaricatum voucher CNU019163 cytochrome c oxidase subunit I (cox1) gene, partial cds; mitochondrial
gi|408722312|gb|JX891588.1|

Nucleotide
Chain A, hemoglobin
Chain A, hemoglobin
gi|18655670|pdb|1IT2|A

Protein
MULTISPECIES: PPE family protein [Mycobacterium]
MULTISPECIES: PPE family protein [Mycobacterium]
gi|685920147|ref|WP_031656710.1|

Protein
MULTISPECIES: Hsp70 family protein [Mycobacterium]
MULTISPECIES: Hsp70 family protein [Mycobacterium]
gi|685918026|ref|WP_031654813.1|

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000806448	PreventionGenetics, part of Exact Sciences	no assertion criteria provided	Pathogenic (Jun 20, 2024)	germline	clinical testing

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000806448

PreventionGenetics, part of Exact Sciences

no assertion criteria provided

Pathogenic
(Jun 20, 2024)

germline

clinical testing

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

Details of each submission

From PreventionGenetics, part of Exact Sciences, SCV000806448.3

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

#	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

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