1-211663459-T-A

Variant summary

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

The NM_002497.4(NEK2):​c.1305A>T​(p.Gln435His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,388 control chromosomes in the GnomAD database, with no homozygous occurrence. 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. Synonymous variant affecting the same amino acid position (i.e. Q435Q) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

NEK2
NM_002497.4 missense

Scores

2
17

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.366

Publications

0 publications found
Variant links:
Genes affected
NEK2 (HGNC:7745): (NIMA related kinase 2) This gene encodes a serine/threonine-protein kinase that is involved in mitotic regulation. This protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. Alternatively spliced transcript variants encoding different isoforms with distinct C-termini have been noted for this gene. [provided by RefSeq, Feb 2011]
NEK2 Gene-Disease associations (from GenCC):
  • retinitis pigmentosa
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • retinitis pigmentosa 67
    Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

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=0.10191691).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEK2NM_002497.4 linkc.1305A>T p.Gln435His missense_variant Exon 8 of 8 ENST00000366999.9 NP_002488.1 P51955-1
NEK2NM_001204182.2 linkc.1111+3647A>T intron_variant Intron 7 of 7 NP_001191111.1 P51955F6U4U2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK2ENST00000366999.9 linkc.1305A>T p.Gln435His missense_variant Exon 8 of 8 1 NM_002497.4 ENSP00000355966.4 P51955-1
NEK2ENST00000540251.5 linkc.1111+3647A>T intron_variant Intron 7 of 7 1 ENSP00000440237.2 F6U4U2
NEK2ENST00000462283.5 linkn.745A>T non_coding_transcript_exon_variant Exon 5 of 5 2
NEK2ENST00000489633.1 linkn.*66A>T downstream_gene_variant 2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461388
Hom.:
0
Cov.:
33
AF XY:
0.00
AC XY:
0
AN XY:
726970
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33470
American (AMR)
AF:
0.00
AC:
0
AN:
44696
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26122
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39700
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86162
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53386
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5762
European-Non Finnish (NFE)
AF:
9.00e-7
AC:
1
AN:
1111716
Other (OTH)
AF:
0.00
AC:
0
AN:
60374
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.14
BayesDel_addAF
Benign
-0.036
T
BayesDel_noAF
Benign
-0.29
CADD
Benign
16
DANN
Benign
0.93
DEOGEN2
Benign
0.12
T
Eigen
Benign
-1.1
Eigen_PC
Benign
-1.1
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.78
T
M_CAP
Benign
0.058
D
MetaRNN
Benign
0.10
T
MetaSVM
Benign
-0.72
T
MutationAssessor
Uncertain
2.1
M
PhyloP100
-0.37
PrimateAI
Uncertain
0.59
T
PROVEAN
Benign
-1.1
N
REVEL
Benign
0.27
Sift
Benign
0.032
D
Sift4G
Benign
0.066
T
Polyphen
0.0
B
Vest4
0.16
MutPred
0.22
Gain of helix (P = 0.0128);
MVP
0.64
MPC
0.37
ClinPred
0.15
T
GERP RS
-2.9
Varity_R
0.041
gMVP
0.19
Mutation Taster
=84/16
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: rs750289918; hg19: chr1-211836801; API