Variant chr1-211670267-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.287

Variant links:

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]

NEK2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

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	Effect	MANE
NEK2	NM_002497.4 linkuse as main transcript	c.765+14G>T	intron_variant	ENST00000366999.9
NEK2	NM_001204182.2 linkuse as main transcript	c.765+14G>T	intron_variant
NEK2	NM_001204183.2 linkuse as main transcript	c.765+14G>T	intron_variant

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Appris	UniProt
NEK2	ENST00000366999.9 linkuse as main transcript	c.765+14G>T	intron_variant	1	NM_002497.4	P1	P51955-1
NEK2	ENST00000366998.4 linkuse as main transcript	c.765+14G>T	intron_variant	1			P51955-2
NEK2	ENST00000540251.5 linkuse as main transcript	c.765+14G>T	intron_variant	1
NEK2	ENST00000462283.5 linkuse as main transcript	n.229+14G>T	intron_variant, non_coding_transcript_variant	2

Frequencies

GnomAD3 genomes

AF:

0.0379

AC:

5775

AN:

152176

Hom.:

227

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0435

AC XY:

31452

AN XY:

722340

show subpopulations

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.:

AF XY:

0.0402

AC XY:

2990

AN XY:

74456

show subpopulations

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.:

Bravo

AF:

0.0378

Asia WGS

AF:

0.152

AC:

527

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jan 31, 2024	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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 -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over