rs2289725

chr1-211670267-C-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_002497.4(NEK2):c.765+14G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0419 in 1,604,186 control chromosomes in the GnomAD database, including 2,304 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.038 (229 hom., cov: 33)
  • Exomes 𝑓: 0.042 (2075 hom.)
• Consequence: NEK2 NM_002497.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.287

Genes affected

NEK2 (HGNC:7745): (NIMA related kinase 2) This gene encodes a serine/threonine-protein kinase that is involved in mitotic regulation. This protein is localized to the centrosome, and undetectable during G1 phase, but accumulates progressively throughout the S phase, reaching maximal levels in late G2 phase. Alternatively spliced transcript variants encoding different isoforms with distinct C-termini have been noted for this gene. [provided by RefSeq, Feb 2011]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BP6: Variant 1-211670267-C-A is Benign according to our data. Variant chr1-211670267-C-A is described in ClinVar as [Benign]. Clinvar id is 403227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.215 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
NEK2	NM_002497.4	c.765+14G>T		intron_variant		ENST00000366999.9
NEK2	NM_001204182.2	c.765+14G>T		intron_variant
NEK2	NM_001204183.2	c.765+14G>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
NEK2	ENST00000366999.9	c.765+14G>T		intron_variant		1	NM_002497.4	P1
NEK2	ENST00000366998.4	c.765+14G>T		intron_variant		1
NEK2	ENST00000540251.5	c.765+14G>T		intron_variant		1
NEK2	ENST00000462283.5	n.229+14G>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0379 AC: 5775 AN: 152176 Hom.: 227 Cov.: 33

Gnomad AFR AF: 0.00796

Gnomad AMI AF: 0.0132

Gnomad AMR AF: 0.0441

Gnomad ASJ AF: 0.0743

Gnomad EAS AF: 0.225

Gnomad SAS AF: 0.0654

Gnomad FIN AF: 0.0372

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0369

Gnomad OTH AF: 0.0392

GnomAD3 exomes AF: 0.0579 AC: 14364 AN: 248146 Hom.: 790 AF XY: 0.0586 AC XY: 7857 AN XY: 134010

Gnomad AFR exome AF: 0.00698

Gnomad AMR exome AF: 0.0461

Gnomad ASJ exome AF: 0.0757

Gnomad EAS exome AF: 0.230

Gnomad SAS exome AF: 0.0668

Gnomad FIN exome AF: 0.0381

Gnomad NFE exome AF: 0.0407

Gnomad OTH exome AF: 0.0559

GnomAD4 exome AF: 0.0423 AC: 61450 AN: 1451892 Hom.: 2075 Cov.: 29 AF XY: 0.0435 AC XY: 31452 AN XY: 722340

Gnomad4 AFR exome AF: 0.00777

Gnomad4 AMR exome AF: 0.0463

Gnomad4 ASJ exome AF: 0.0758

Gnomad4 EAS exome AF: 0.199

Gnomad4 SAS exome AF: 0.0634

Gnomad4 FIN exome AF: 0.0381

Gnomad4 NFE exome AF: 0.0346

Gnomad4 OTH exome AF: 0.0542

GnomAD4 genome AF: 0.0379 AC: 5777 AN: 152294 Hom.: 229 Cov.: 33 AF XY: 0.0402 AC XY: 2990 AN XY: 74456

Gnomad4 AFR AF: 0.00796

Gnomad4 AMR AF: 0.0440

Gnomad4 ASJ AF: 0.0743

Gnomad4 EAS AF: 0.226

Gnomad4 SAS AF: 0.0653

Gnomad4 FIN AF: 0.0372

Gnomad4 NFE AF: 0.0369

Gnomad4 OTH AF: 0.0388

Alfa AF: 0.0417 Hom.: 56

Bravo AF: 0.0378

Asia WGS AF: 0.152 AC: 527 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jan 31, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
Cadd	Benign	5.6
Dann	Benign	0.66

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

LitVar

Other links and lift over

dbSNP: rs2289725; hg19: chr1-211843609; COSMIC: COSV65355209; COSMIC: COSV65355209;