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NM_002485.5(NBN):c.539T>G (p.Phe180Cys) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 18, 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:
RCV000462336.8

Allele description [Variation Report for NM_002485.5(NBN):c.539T>G (p.Phe180Cys)]

NM_002485.5(NBN):c.539T>G (p.Phe180Cys)

Gene:
NBN:nibrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_002485.5(NBN):c.539T>G (p.Phe180Cys)
HGVS:
  • NC_000008.11:g.89978265A>C
  • NG_008860.1:g.11407T>G
  • NM_001024688.3:c.293T>G
  • NM_002485.5:c.539T>GMANE SELECT
  • NP_001019859.1:p.Phe98Cys
  • NP_002476.2:p.Phe180Cys
  • NP_002476.2:p.Phe180Cys
  • LRG_158t1:c.539T>G
  • LRG_158:g.11407T>G
  • LRG_158p1:p.Phe180Cys
  • NC_000008.10:g.90990493A>C
  • NM_002485.4:c.539T>G
Protein change:
F180C
Links:
dbSNP: rs1060503457
NCBI 1000 Genomes Browser:
rs1060503457
Molecular consequence:
  • NM_001024688.3:c.293T>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002485.5:c.539T>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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000553048Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Oct 18, 2021) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical 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, SCV000553048.8

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 411744). This variant has not been reported in the literature in individuals affected with NBN-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces phenylalanine with cysteine at codon 180 of the NBN protein (p.Phe180Cys). The phenylalanine residue is weakly conserved and there is a large physicochemical difference between phenylalanine and cysteine.

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

Last Updated: Sep 29, 2024