chr17-28729008-C-T

Variant names:

• chr17-28729008-C-T
• rs7211220
• NM_178170.3:c.47+148C>T

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+148C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0964 in 726,040 control chromosomes in the GnomAD database, including 3,881 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.10 (819 hom., cov: 33)
  • Exomes 𝑓: 0.095 (3062 hom.)
• Consequence: NEK8 NM_178170.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.504
• 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=-0.7).
• BP6: Variant 17-28729008-C-T is Benign according to our data. Variant chr17-28729008-C-T is described in ClinVar as [Benign]. Clinvar id is 1296813.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+148C>T		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+148C>T		intron_variant	Intron 1 of 14	1	NM_178170.3	ENSP00000268766.6

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15398 AN: 152206 Hom.: 818 Cov.: 33

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.0844

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: 0.0862

Gnomad OTH AF: 0.0989

GnomAD4 exome AF: 0.0951 AC: 54563 AN: 573716 Hom.: 3062 AF XY: 0.0972 AC XY: 29461 AN XY: 303210

African (AFR) AF: 0.127 AC: 1980 AN: 15618

American (AMR) AF: 0.0649 AC: 1872 AN: 28862

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 2230 AN: 17024

East Asian (EAS) AF: 0.162 AC: 5155 AN: 31838

South Asian (SAS) AF: 0.147 AC: 8345 AN: 56602

European-Finnish (FIN) AF: 0.0774 AC: 2763 AN: 35686

Middle Eastern (MID) AF: 0.132 AC: 347 AN: 2622

European-Non Finnish (NFE) AF: 0.0818 AC: 29046 AN: 355078

Other (OTH) AF: 0.0930 AC: 2825 AN: 30386

GnomAD4 genome AF: 0.101 AC: 15402 AN: 152324 Hom.: 819 Cov.: 33 AF XY: 0.101 AC XY: 7543 AN XY: 74488

African (AFR) AF: 0.125 AC: 5190 AN: 41570

American (AMR) AF: 0.0849 AC: 1300 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3468

East Asian (EAS) AF: 0.125 AC: 649 AN: 5186

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

European-Finnish (FIN) AF: 0.0773 AC: 821 AN: 10616

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

European-Non Finnish (NFE) AF: 0.0862 AC: 5864 AN: 68022

Other (OTH) AF: 0.0983 AC: 208 AN: 2116

Alfa AF: 0.0591 Hom.: 74

Bravo AF: 0.102

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	7.3
DANN	Benign	0.72
PhyloP100		0.50
PromoterAI		-0.00010	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: rs7211220; hg19: chr17-27056026; COSMIC: COSV52045569; COSMIC: COSV52045569;