17-28728880-G-T

Variant names:

• chr17-28728880-G-T
• rs776304725
• NM_178170.3:c.47+20G>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_178170.3(NEK8):​c.47+20G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: NEK8 NM_178170.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.11
• Publications: 0 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 17-28728880-G-T is Benign according to our data. Variant chr17-28728880-G-T is described in ClinVar as [Likely_benign]. Clinvar id is 2754489.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK8	NM_178170.3	c.47+20G>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+20G>T		intron_variant	Intron 1 of 14	1	NM_178170.3	ENSP00000268766.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1392670 Hom.: 0 Cov.: 29 AF XY: 0.00 AC XY: 0 AN XY: 687326

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: 0.00 AC: 0 AN: 57780

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Nephronophthisis 9 Benign:1

Nov 03, 2023

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	15
DANN	Benign	0.81
PhyloP100		2.1
PromoterAI		0.042	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: rs776304725; hg19: chr17-27055898;