NM_002497.4:c.1317A>G

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.1317A>G(p.Arg439Arg) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 1,612,166 control chromosomes in the GnomAD database, including 51,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.28 ( 6530 hom., cov: 32)

Exomes 𝑓: 0.24 ( 44960 hom. )

Consequence

NEK2
NM_002497.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -1.01

Publications

15 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=-0.82).

BP6

Variant 1-211663447-T-C is Benign according to our data. Variant chr1-211663447-T-C is described in ClinVar as [Benign]. Clinvar id is 403226.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.365 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
NEK2	NM_002497.4 link	c.1317A>G	p.Arg439Arg	synonymous_variant	Exon 8 of 8	ENST00000366999.9	NP_002488.1	P51955-1
NEK2	NM_001204182.2 link	c.1111+3659A>G		intron_variant	Intron 7 of 7		NP_001191111.1	P51955F6U4U2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
NEK2	ENST00000366999.9 link	c.1317A>G	p.Arg439Arg	synonymous_variant	Exon 8 of 8	1	NM_002497.4	ENSP00000355966.4	P51955-1
NEK2	ENST00000540251.5 link	c.1111+3659A>G		intron_variant	Intron 7 of 7	1		ENSP00000440237.2	F6U4U2
NEK2	ENST00000462283.5 link	n.757A>G		non_coding_transcript_exon_variant	Exon 5 of 5	2
NEK2	ENST00000489633.1 link	n.*78A>G		downstream_gene_variant		2

Frequencies

GnomAD3 genomes

AF:

0.285

AC:

43271

AN:

151988

Hom.:

6510

Cov.:

show subpopulations

Gnomad AFR

AF:

0.370

Gnomad AMI

AF:

0.301

Gnomad AMR

AF:

0.319

Gnomad ASJ

AF:

0.209

Gnomad EAS

AF:

0.261

Gnomad SAS

AF:

0.299

Gnomad FIN

AF:

0.247

Gnomad MID

AF:

0.190

Gnomad NFE

AF:

0.236

Gnomad OTH

AF:

0.274

GnomAD2 exomes

AF:

0.268

AC:

66655

AN:

248272

AF XY:

0.262

show subpopulations

Gnomad AFR exome

AF:

0.378

Gnomad AMR exome

AF:

0.352

Gnomad ASJ exome

AF:

0.217

Gnomad EAS exome

AF:

0.273

Gnomad FIN exome

AF:

0.259

Gnomad NFE exome

AF:

0.230

Gnomad OTH exome

AF:

0.259

GnomAD4 exome

AF:

0.245

AC:

357711

AN:

1460060

Hom.:

44960

Cov.:

AF XY:

0.245

AC XY:

177565

AN XY:

726172

show subpopulations

African (AFR)

AF:

0.376

AC:

12586

AN:

33458

American (AMR)

AF:

0.349

AC:

15521

AN:

44494

Ashkenazi Jewish (ASJ)

AF:

0.217

AC:

5658

AN:

26102

East Asian (EAS)

AF:

0.272

AC:

10796

AN:

39680

South Asian (SAS)

AF:

0.281

AC:

24170

AN:

85968

European-Finnish (FIN)

AF:

0.259

AC:

13801

AN:

53310

Middle Eastern (MID)

AF:

0.219

AC:

1257

AN:

5752

European-Non Finnish (NFE)

AF:

0.233

AC:

258612

AN:

1110986

Other (OTH)

AF:

0.254

AC:

15310

AN:

60310

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

15493

30986

46478

61971

77464

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.285

AC:

43342

AN:

152106

Hom.:

6530

Cov.:

AF XY:

0.284

AC XY:

21132

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.370

AC:

15338

AN:

41460

American (AMR)

AF:

0.319

AC:

4880

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.209

AC:

727

AN:

3472

East Asian (EAS)

AF:

0.260

AC:

1346

AN:

5170

South Asian (SAS)

AF:

0.299

AC:

1443

AN:

4822

European-Finnish (FIN)

AF:

0.247

AC:

2609

AN:

10580

Middle Eastern (MID)

AF:

0.197

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.236

AC:

16083

AN:

68008

Other (OTH)

AF:

0.277

AC:

584

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1578

3156

4733

6311

7889

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.253

Hom.:

2181

Bravo

AF:

0.292

Asia WGS

AF:

0.325

AC:

1130

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

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 -

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

-0.82

CADD

Benign

4.2

(source)

DANN

Benign

0.67

PhyloP100

-1.0

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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NM_002497.4:c.1317A>G

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