NM_002485.5(NBN):c.1566_1568del (p.Leu522del) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Feb 2, 2022
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:: RCV002991753.3

Allele description [Variation Report for NM_002485.5(NBN):c.1566_1568del (p.Leu522del)]

NM_002485.5(NBN):c.1566_1568del (p.Leu522del)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.1566_1568del (p.Leu522del)

HGVS:

NC_000008.11:g.89953523_89953525del
NG_008860.1:g.36149_36151del
NM_001024688.3:c.1320_1322del
NM_002485.5:c.1566_1568delMANE SELECT
NP_001019859.1:p.Leu440del
NP_002476.2:p.Leu522del
NP_002476.2:p.Leu522del
LRG_158t1:c.1564_1566del
LRG_158:g.36149_36151del
LRG_158p1:p.Leu522del
NC_000008.10:g.90965749_90965751del
NC_000008.10:g.90965751_90965753del
NM_002485.4:c.1564_1566delTTA

Protein change:

L440del

Molecular consequence:

NM_001024688.3:c.1320_1322del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_002485.5:c.1566_1568del - inframe_deletion - [Sequence Ontology: SO:0001822]

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

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P-loop containing nucleoside triphosphate hydrolases superfamily protein [Arabid...
P-loop containing nucleoside triphosphate hydrolases superfamily protein [Arabidopsis thaliana]
gi|334185474|ref|NP_188608.4|

Protein
AAA-type ATPase family protein [Arabidopsis thaliana]
AAA-type ATPase family protein [Arabidopsis thaliana]
gi|334182249|ref|NP_171788.3|

Protein
CAT [Nothoprocta perdicaria]
CAT [Nothoprocta perdicaria]
Gene ID:112943474

Gene
UGT8 [Nothoprocta perdicaria]
UGT8 [Nothoprocta perdicaria]
Gene ID:112943430

Gene
Protein Structure, Secondary
Protein Structure, Secondary
The level of protein structure in which regular hydrogen-bond interactions within contiguous stretches of polypeptide chain give rise to ALPHA-HELICES; BETA-STRANDS (which ali...<br/>Year introduced: 1993

MeSH

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003310738	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Feb 2, 2022)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003310738

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Feb 2, 2022)

germline

clinical testing

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

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

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV003310738.2

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

Description

This variant is not present in population databases (gnomAD no frequency). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant, c.1566_1568del, results in the deletion of 1 amino acid(s) of the NBN protein (p.Leu522del), but otherwise preserves the integrity of the reading frame.

#	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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