NM_002485.5(NBN):c.628G>A (p.Val210Ile) AND Microcephaly, normal intelligence and immunodeficiency

This record was updated by the submitter. Please see the current version.

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Aug 26, 2021
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:: RCV001876175.6

Allele description

NM_002485.5(NBN):c.628G>A (p.Val210Ile)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.628G>A (p.Val210Ile)

HGVS:

NC_000008.11:g.89971247C>T
NG_008860.1:g.18425G>A
NM_001024688.3:c.382G>A
NM_002485.5:c.628G>AMANE SELECT
NP_001019859.1:p.Val128Ile
NP_002476.2:p.Val210Ile
LRG_158t1:c.628G>A
LRG_158:g.18425G>A
NC_000008.10:g.90983475C>T
NC_000008.10:g.90983475C>T

Protein change:

V128I

Links:

dbSNP: rs61754796

NCBI 1000 Genomes Browser:

rs61754796

Molecular consequence:

NM_001024688.3:c.382G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.628G>A - missense variant - [Sequence Ontology: SO:0001583]

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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Colletotrichum cliviicola isolate YSY-2-2 calmodulin (CAL) gene, partial cds
Colletotrichum cliviicola isolate YSY-2-2 calmodulin (CAL) gene, partial cds
gi|2161158939|gb|MW046781.1|

Nucleotide
LINE-1 retrotransposable element ORF2 protein isoform X2 [Bactrocera dorsalis]
LINE-1 retrotransposable element ORF2 protein isoform X2 [Bactrocera dorsalis]
gi|2273979509|ref|XP_049316705.1|

Protein
Homo sapiens Myb/SANT DNA binding domain containing 2 (MSANTD2), transcript vari...
Homo sapiens Myb/SANT DNA binding domain containing 2 (MSANTD2), transcript variant 3, mRNA
gi|1677530418|ref|NM_001308027.2|

Nucleotide
calmodulin, partial [Colletotrichum fructicola]
calmodulin, partial [Colletotrichum fructicola]
gi|2161158916|gb|UFY86023.1|

Protein
Homo sapiens serine rich and transmembrane domain containing 1 (SERTM1), mRNA
Homo sapiens serine rich and transmembrane domain containing 1 (SERTM1), mRNA
gi|1519314177|ref|NM_203451.3|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002308321	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Aug 26, 2021)	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

SCV002308321

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Aug 26, 2021)

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 Invitae, SCV002308321.2

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

Description

This sequence change replaces valine with isoleucine at codon 210 of the NBN protein (p.Val210Ile). The valine residue is weakly conserved and there is a small physicochemical difference between valine and isoleucine. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals affected with NBN-related conditions. ClinVar contains an entry for this variant (Variation ID: 924457). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The isoleucine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.

#	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 16, 2024

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Relating variation to medicine