8-89953435-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_002485.5(NBN):​c.1654G>A​(p.Glu552Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E552Q) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

NBN
NM_002485.5 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.252

Publications

0 publications found
Variant links:
Genes affected
NBN (HGNC:7652): (nibrin) Mutations in this gene are associated with Nijmegen breakage syndrome, an autosomal recessive chromosomal instability syndrome characterized by microcephaly, growth retardation, immunodeficiency, and cancer predisposition. The encoded protein is a member of the MRE11/RAD50 double-strand break repair complex which consists of 5 proteins. This gene product is thought to be involved in DNA double-strand break repair and DNA damage-induced checkpoint activation. [provided by RefSeq, Jul 2008]
NBN Gene-Disease associations (from GenCC):
  • Nijmegen breakage syndrome
    Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Orphanet, Labcorp Genetics (formerly Invitae), ClinGen, Myriad Women’s Health
  • rhabdomyosarcoma
    Inheritance: AR Classification: MODERATE Submitted by: Genomics England PanelApp
  • idiopathic aplastic anemia
    Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)
  • prostate cancer
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
  • hereditary breast carcinoma
    Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.124360085).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NBNNM_002485.5 linkc.1654G>A p.Glu552Lys missense_variant Exon 11 of 16 ENST00000265433.8 NP_002476.2 O60934

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NBNENST00000265433.8 linkc.1654G>A p.Glu552Lys missense_variant Exon 11 of 16 1 NM_002485.5 ENSP00000265433.4 O60934

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
32
GnomAD4 genome
Cov.:
32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.082
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
12
DANN
Uncertain
0.99
DEOGEN2
Benign
0.091
T;T
Eigen
Benign
-0.19
Eigen_PC
Benign
-0.13
FATHMM_MKL
Benign
0.39
N
LIST_S2
Benign
0.67
T;T
M_CAP
Benign
0.023
T
MetaRNN
Benign
0.12
T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Benign
2.0
M;.
PhyloP100
0.25
PrimateAI
Benign
0.39
T
PROVEAN
Benign
-0.41
N;N
REVEL
Benign
0.019
Sift
Benign
0.18
T;T
Sift4G
Benign
0.39
T;T
Polyphen
0.88
P;.
Vest4
0.16
MutPred
0.30
Gain of MoRF binding (P = 0.0084);.;
MVP
0.76
MPC
0.15
ClinPred
0.24
T
GERP RS
3.3
PromoterAI
-0.010
Neutral
Varity_R
0.059
gMVP
0.32
Mutation Taster
=97/3
polymorphism

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs1064793213; hg19: chr8-90965663; API