chr17-28729007-C-A

Variant names:

• chr17-28729007-C-A
• rs7211214
• NM_178170.3:c.47+147C>A

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_178170.3(NEK8):​c.47+147C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0975 in 726,114 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (868 hom., cov: 33)
  • Exomes 𝑓: 0.096 (3092 hom.)
• Consequence: NEK8 NM_178170.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.65
• 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 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

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 17-28729007-C-A is Benign according to our data. Variant chr17-28729007-C-A is described in ClinVar as [Benign]. Clinvar id is 1274047.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.145 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK8	NM_178170.3	c.47+147C>A		intron_variant	Intron 1 of 14	ENST00000268766.11	NP_835464.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
NEK8	ENST00000268766.11	c.47+147C>A		intron_variant	Intron 1 of 14	1	NM_178170.3	ENSP00000268766.6

Frequencies

GnomAD3 genomes AF: 0.103 AC: 15739 AN: 152202 Hom.: 866 Cov.: 33

Gnomad AFR AF: 0.132

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0858

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.125

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0773

Gnomad MID AF: 0.130

Gnomad NFE AF: 0.0864

Gnomad OTH AF: 0.101

GnomAD4 exome AF: 0.0959 AC: 55013 AN: 573794 Hom.: 3092 AF XY: 0.0979 AC XY: 29691 AN XY: 303278

African (AFR) AF: 0.135 AC: 2104 AN: 15598

American (AMR) AF: 0.0661 AC: 1905 AN: 28832

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 2239 AN: 17008

East Asian (EAS) AF: 0.162 AC: 5154 AN: 31840

South Asian (SAS) AF: 0.148 AC: 8369 AN: 56628

European-Finnish (FIN) AF: 0.0776 AC: 2774 AN: 35738

Middle Eastern (MID) AF: 0.134 AC: 351 AN: 2622

European-Non Finnish (NFE) AF: 0.0823 AC: 29241 AN: 355132

Other (OTH) AF: 0.0946 AC: 2876 AN: 30396

GnomAD4 genome AF: 0.103 AC: 15752 AN: 152320 Hom.: 868 Cov.: 33 AF XY: 0.103 AC XY: 7699 AN XY: 74476

African (AFR) AF: 0.132 AC: 5505 AN: 41566

American (AMR) AF: 0.0863 AC: 1321 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.125 AC: 649 AN: 5184

South Asian (SAS) AF: 0.154 AC: 743 AN: 4832

European-Finnish (FIN) AF: 0.0773 AC: 821 AN: 10622

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.0864 AC: 5874 AN: 68016

Other (OTH) AF: 0.100 AC: 212 AN: 2116

Alfa AF: 0.0387 Hom.: 24

Bravo AF: 0.105

Asia WGS AF: 0.131 AC: 456 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.0080
DANN	Benign	0.70
PhyloP100		-4.7
PromoterAI		-0.019	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs7211214; hg19: chr17-27056025; COSMIC: COSV52047649; COSMIC: COSV52047649;