chr17-28728861-G-A
Variant names:
Variant summary
Our verdict is Pathogenic. The variant received 11 ACMG points: 11P and 0B. PVS1PM2PP5
The NM_178170.3(NEK8):c.47+1G>A variant causes a splice donor, intron change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. 3/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Pathogenic (no stars).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
NEK8
NM_178170.3 splice_donor, intron
NM_178170.3 splice_donor, intron
Scores
5
1
1
Splicing: ADA: 1.000
2
Clinical Significance
Conservation
PhyloP100: 6.09
Publications
2 publications found
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 2Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: ClinGen, G2P, Ambry Genetics
- autosomal dominant polycystic kidney diseaseInheritance: AD Classification: STRONG Submitted by: ClinGen
- nephronophthisis 9Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
- polycystic kidney disease 8Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics
- nephronophthisis 2Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
- renal-hepatic-pancreatic dysplasiaInheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Pathogenic. The variant received 11 ACMG points.
PVS1
Splicing +-2 bp (donor or acceptor) variant, LoF is a know mechanism of disease, Cryptic splice site detected, with MaxEntScore 4, offset of -10, new splice context is: gagGTgcct. Cryptic site results in frameshift change. If cryptic site found is not functional and variant results in exon loss, it results in frameshift change.
PM2
Very rare variant in population databases, with high coverage;
PP5
Variant 17-28728861-G-A is Pathogenic according to our data. Variant chr17-28728861-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 490182.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes Cov.: 33
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1398200Hom.: 0 Cov.: 30 AF XY: 0.00 AC XY: 0AN XY: 689720
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1398200
Hom.:
Cov.:
30
AF XY:
AC XY:
0
AN XY:
689720
African (AFR)
AF:
AC:
0
AN:
31572
American (AMR)
AF:
AC:
0
AN:
35718
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
25166
East Asian (EAS)
AF:
AC:
0
AN:
35746
South Asian (SAS)
AF:
AC:
0
AN:
79210
European-Finnish (FIN)
AF:
AC:
0
AN:
49156
Middle Eastern (MID)
AF:
AC:
0
AN:
5696
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1077962
Other (OTH)
AF:
AC:
0
AN:
57974
GnomAD4 genome Cov.: 33
GnomAD4 genome
Cov.:
33
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
Renal-hepatic-pancreatic dysplasia 2 Pathogenic:1
Feb 14, 2018
OMIM
Significance:Pathogenic
Review Status:no assertion criteria provided
Collection Method:literature only
- -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
DANN
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
PhyloP100
GERP RS
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Pathogenic
dbscSNV1_RF
Pathogenic
SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_DG_spliceai
Position offset: -40
DS_DL_spliceai
Position offset: -1
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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