U.S. flag

An official website of the United States government

NM_002485.5(NBN):c.550G>T (p.Val184Phe) AND Microcephaly, normal intelligence and immunodeficiency

Germline classification:
Uncertain significance (3 submissions)
Last evaluated:
Jul 21, 2022
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:
RCV000636731.11

Allele description [Variation Report for NM_002485.5(NBN):c.550G>T (p.Val184Phe)]

NM_002485.5(NBN):c.550G>T (p.Val184Phe)

Gene:
NBN:nibrin [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
8q21.3
Genomic location:
Preferred name:
NM_002485.5(NBN):c.550G>T (p.Val184Phe)
HGVS:
  • NC_000008.11:g.89978254C>A
  • NG_008860.1:g.11418G>T
  • NM_001024688.3:c.304G>T
  • NM_002485.5:c.550G>TMANE SELECT
  • NP_001019859.1:p.Val102Phe
  • NP_002476.2:p.Val184Phe
  • NP_002476.2:p.Val184Phe
  • LRG_158t1:c.550G>T
  • LRG_158:g.11418G>T
  • LRG_158p1:p.Val184Phe
  • NC_000008.10:g.90990482C>A
  • NM_002485.4:c.550G>T
Protein change:
V102F
Links:
dbSNP: rs1554566641
NCBI 1000 Genomes Browser:
rs1554566641
Molecular consequence:
  • NM_001024688.3:c.304G>T - missense variant - [Sequence Ontology: SO:0001583]
  • NM_002485.5:c.550G>T - 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

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000758171Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Feb 11, 2022)
germlineclinical testing

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

SCV002045178Genome-Nilou Lab
criteria provided, single submitter

(ACMG Guidelines, 2015)
Uncertain significance
(Nov 7, 2021)
germlineclinical testing

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

SCV002584756St. Jude Molecular Pathology, St. Jude Children's Research Hospital
criteria provided, single submitter

(St. Jude Assertion Criteria 2020)
Uncertain significance
(Jul 21, 2022)
germlineclinical testing

Citation Link

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlinenonot providednot providednot providednot providednot providedclinical testing
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

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, SCV000758171.4

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

Description

This sequence change replaces valine, which is neutral and non-polar, with phenylalanine, which is neutral and non-polar, at codon 184 of the NBN protein (p.Val184Phe). This variant is not present in population databases (gnomAD 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: 530734). 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: "Possibly Damaging"; Align-GVGD: "Class C0"). 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.

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

From Genome-Nilou Lab, SCV002045178.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlinenonot providednot providednot providednot providednot providednot providednot provided

From St. Jude Molecular Pathology, St. Jude Children's Research Hospital, SCV002584756.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

The NBN c.550G>T (p.Val184Phe) missense change is absent in gnomAD v2.1.1 (https://gnomad.broadinstitute.org/). The in silico tool REVEL is inconclusive about a pathogenic or benign effect of this variant on protein function, and to our knowledge functional studies have not been performed. To our knowledge, this variant has not been reported in individuals with Nijmegan breakage syndrome or NBN-associated cancers. In summary, the evidence currently available is insufficient to determine the clinical significance of this variant. It has therefore been classified as of uncertain significance.

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

Last Updated: Sep 29, 2024