NM_002485.5(NBN):c.2197C>G (p.His733Asp) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Nov 2, 2023
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:: RCV001059710.12

Allele description [Variation Report for NM_002485.5(NBN):c.2197C>G (p.His733Asp)]

NM_002485.5(NBN):c.2197C>G (p.His733Asp)

Gene:

NBN:nibrin [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

8q21.3

Genomic location:

Preferred name:

NM_002485.5(NBN):c.2197C>G (p.His733Asp)

HGVS:

NC_000008.11:g.89937063G>C
NG_008860.1:g.52609C>G
NM_001024688.3:c.1951C>G
NM_002485.5:c.2197C>GMANE SELECT
NP_001019859.1:p.His651Asp
NP_002476.2:p.His733Asp
NP_002476.2:p.His733Asp
LRG_158t1:c.2197C>G
LRG_158:g.52609C>G
LRG_158p1:p.His733Asp
NC_000008.10:g.90949291G>C
NM_002485.4:c.2197C>G

Protein change:

H651D

Links:

dbSNP: rs1311278427

NCBI 1000 Genomes Browser:

rs1311278427

Molecular consequence:

NM_001024688.3:c.1951C>G - missense variant - [Sequence Ontology: SO:0001583]
NM_002485.5:c.2197C>G - 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

Clear Turn Off Turn On

protein TALPID3 isoform X14 [Homo sapiens]
protein TALPID3 isoform X14 [Homo sapiens]
gi|2217299137|ref|XP_047287966.1|

Protein
Incest
Incest
Sexual intercourse between persons so closely related that they are forbidden by law to marry.<br/>Year introduced: 1967

MeSH
High-Frequency Jet Ventilation
High-Frequency Jet Ventilation
Respiratory support system used primarily with rates of about 100 to 200/min with volumes of from about one to three times predicted anatomic dead space. Used to treat respira...<br/>Year introduced: 1988

MeSH
Brachial Plexus Neuritis
Brachial Plexus Neuritis
A syndrome associated with inflammation of the BRACHIAL PLEXUS. Clinical features include severe pain in the shoulder region which may be accompanied by MUSCLE WEAKNESS and lo...<br/>Year introduced: 2000

MeSH
Myocardial Revascularization
Myocardial Revascularization
The restoration of blood supply to the myocardium. (From Dorland, 28th ed)<br/>Year introduced: 1973

MeSH

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001224348	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Nov 2, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]
SCV002046037	Genome-Nilou Lab	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Nov 7, 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

SCV001224348

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Nov 2, 2023)

germline

clinical testing

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

SCV002046037

Genome-Nilou Lab

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Nov 7, 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	no	not provided	not provided	not provided	not provided	not provided	clinical testing
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

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

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001224348.7

#	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 histidine, which is basic and polar, with aspartic acid, which is acidic and polar, at codon 733 of the NBN protein (p.His733Asp). This variant is present in population databases (no rsID available, gnomAD 0.3%). 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: 627828). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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

From Genome-Nilou Lab, SCV002046037.1

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

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	no	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Sep 29, 2024

ClinVar

Relating variation to medicine