17-28728880-G-C

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_178170.3(NEK8):​c.47+20G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000718 in 1,392,670 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.2e-7 ( 0 hom. )

Consequence

NEK8
NM_178170.3 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.11

Publications

0 publications found
Variant links:
Genes affected
NEK8 (HGNC:13387): (NIMA related kinase 8) This gene encodes a member of the serine/threionine protein kinase family related to NIMA (never in mitosis, gene A) of Aspergillus nidulans. The encoded protein may play a role in cell cycle progression from G2 to M phase. Mutations in the related mouse gene are associated with a disease phenotype that closely parallels the juvenile autosomal recessive form of polycystic kidney disease in humans. [provided by RefSeq, Jul 2008]
NEK8 Gene-Disease associations (from GenCC):
  • renal-hepatic-pancreatic dysplasia 2
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics
  • autosomal dominant polycystic kidney disease
    Inheritance: AD Classification: STRONG Submitted by: ClinGen
  • nephronophthisis 9
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • polycystic kidney disease 8
    Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
  • nephronophthisis 2
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
  • renal-hepatic-pancreatic dysplasia
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.62).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
NEK8NM_178170.3 linkc.47+20G>C intron_variant Intron 1 of 14 ENST00000268766.11 NP_835464.1 Q86SG6

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
NEK8ENST00000268766.11 linkc.47+20G>C intron_variant Intron 1 of 14 1 NM_178170.3 ENSP00000268766.6 Q86SG6

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
7.18e-7
AC:
1
AN:
1392670
Hom.:
0
Cov.:
29
AF XY:
0.00000145
AC XY:
1
AN XY:
687326
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
31474
American (AMR)
AF:
0.00
AC:
0
AN:
35704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25126
East Asian (EAS)
AF:
0.00
AC:
0
AN:
35708
South Asian (SAS)
AF:
0.00
AC:
0
AN:
79118
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
49066
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5688
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1073006
Other (OTH)
AF:
0.0000173
AC:
1
AN:
57780
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
BayesDel_noAF
Benign
-0.62
CADD
Benign
15
DANN
Benign
0.74
PhyloP100
2.1
PromoterAI
-0.069
Neutral

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: rs776304725; hg19: chr17-27055898; API