rs701929

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_002497.4(NEK2):c.504T>C(p.His168His) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.511 in 1,613,692 control chromosomes in the GnomAD database, including 215,163 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.54 ( 22444 hom., cov: 33)

Exomes 𝑓: 0.51 ( 192719 hom. )

Consequence

NEK2
NM_002497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.573

Publications

26 publications found

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 Gene-Disease associations (from GenCC):

retinitis pigmentosa
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
retinitis pigmentosa 67
Inheritance: AR, Unknown Classification: LIMITED Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)

NEK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 1-211673534-A-G is Benign according to our data. Variant chr1-211673534-A-G is described in ClinVar as Benign. ClinVar VariationId is 403228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.573 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
NEK2	NM_002497.4 link	c.504T>C	p.His168His	synonymous_variant	Exon 3 of 8	ENST00000366999.9	NP_002488.1
NEK2	NM_001204182.2 link	c.504T>C	p.His168His	synonymous_variant	Exon 3 of 8		NP_001191111.1
NEK2	NM_001204183.2 link	c.504T>C	p.His168His	synonymous_variant	Exon 3 of 7		NP_001191112.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein
NEK2	ENST00000366999.9 link	c.504T>C	p.His168His	synonymous_variant	Exon 3 of 8	1	NM_002497.4	ENSP00000355966.4
NEK2	ENST00000540251.5 link	c.504T>C	p.His168His	synonymous_variant	Exon 3 of 8	1		ENSP00000440237.2
NEK2	ENST00000366998.4 link	c.504T>C	p.His168His	synonymous_variant	Exon 3 of 7	1		ENSP00000355965.3

Frequencies

GnomAD3 genomes

AF:

0.538

AC:

81766

AN:

151964

Hom.:

22412

Cov.:

show subpopulations

Gnomad AFR

AF:

0.540

Gnomad AMI

AF:

0.611

Gnomad AMR

AF:

0.641

Gnomad ASJ

AF:

0.493

Gnomad EAS

AF:

0.731

Gnomad SAS

AF:

0.632

Gnomad FIN

AF:

0.575

Gnomad MID

AF:

0.500

Gnomad NFE

AF:

0.488

Gnomad OTH

AF:

0.538

GnomAD2 exomes

AF:

0.567

AC:

142349

AN:

251222

AF XY:

0.563

show subpopulations

Gnomad AFR exome

AF:

0.543

Gnomad AMR exome

AF:

0.733

Gnomad ASJ exome

AF:

0.481

Gnomad EAS exome

AF:

0.729

Gnomad FIN exome

AF:

0.580

Gnomad NFE exome

AF:

0.481

Gnomad OTH exome

AF:

0.543

GnomAD4 exome

AF:

0.508

AC:

742295

AN:

1461608

Hom.:

192719

Cov.:

AF XY:

0.511

AC XY:

371273

AN XY:

727116

show subpopulations

African (AFR)

AF:

0.535

AC:

17915

AN:

33472

American (AMR)

AF:

0.721

AC:

32241

AN:

44716

Ashkenazi Jewish (ASJ)

AF:

0.485

AC:

12674

AN:

26132

East Asian (EAS)

AF:

0.741

AC:

29415

AN:

39700

South Asian (SAS)

AF:

0.628

AC:

54181

AN:

86252

European-Finnish (FIN)

AF:

0.580

AC:

30986

AN:

53410

Middle Eastern (MID)

AF:

0.507

AC:

2924

AN:

5764

European-Non Finnish (NFE)

AF:

0.477

AC:

530566

AN:

1111782

Other (OTH)

AF:

0.520

AC:

31393

AN:

60380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

20466

40932

61398

81864

102330

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15868

31736

47604

63472

79340

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.538

AC:

81846

AN:

152084

Hom.:

22444

Cov.:

AF XY:

0.545

AC XY:

40522

AN XY:

74332

show subpopulations

African (AFR)

AF:

0.540

AC:

22394

AN:

41458

American (AMR)

AF:

0.641

AC:

9809

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.493

AC:

1712

AN:

3472

East Asian (EAS)

AF:

0.730

AC:

3783

AN:

5182

South Asian (SAS)

AF:

0.631

AC:

3042

AN:

4818

European-Finnish (FIN)

AF:

0.575

AC:

6083

AN:

10576

Middle Eastern (MID)

AF:

0.497

AC:

146

AN:

294

European-Non Finnish (NFE)

AF:

0.488

AC:

33170

AN:

67968

Other (OTH)

AF:

0.545

AC:

1152

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1914

3827

5741

7654

9568

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

716

1432

2148

2864

3580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.507

Hom.:

9110

Bravo

AF:

0.541

Asia WGS

AF:

0.665

AC:

2309

AN:

3478

EpiCase

AF:

0.475

EpiControl

AF:

0.480

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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 -

Retinitis pigmentosa 67

Benign:1

Sep 05, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Retinal dystrophy

Benign:1

Oct 01, 2023

Dept Of Ophthalmology, Nagoya University

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:research

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

0.080

(source)

DANN

Benign

0.53

PhyloP100

-0.57

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over