dbSNP rs2289725: NEK2:c.765+14G>T (chr1-211670267-C-A) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -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

Publications

2 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: Unknown, AR Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics

NEK2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_002497.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002497.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEK2	NM_002497.4	MANE Select	c.765+14G>T	intron	N/A	NP_002488.1	P51955-1
NEK2	NM_001204182.2		c.765+14G>T	intron	N/A	NP_001191111.1	F6U4U2
NEK2	NM_001204183.2		c.765+14G>T	intron	N/A	NP_001191112.1	P51955-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
NEK2	ENST00000366999.9	TSL:1 MANE Select	c.765+14G>T	intron	N/A	ENSP00000355966.4	P51955-1
NEK2	ENST00000540251.5	TSL:1	c.765+14G>T	intron	N/A	ENSP00000440237.2	F6U4U2
NEK2	ENST00000366998.4	TSL:1	c.765+14G>T	intron	N/A	ENSP00000355965.3	P51955-2

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

GnomAD2 exomes

AF:

0.0579

AC:

14364

AN:

248146

AF XY:

0.0586

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 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

African (AFR)

AF:

0.00777

AC:

258

AN:

33200

American (AMR)

AF:

0.0463

AC:

2042

AN:

44136

Ashkenazi Jewish (ASJ)

AF:

0.0758

AC:

1971

AN:

25992

East Asian (EAS)

AF:

0.199

AC:

7882

AN:

39586

South Asian (SAS)

AF:

0.0634

AC:

5395

AN:

85038

European-Finnish (FIN)

AF:

0.0381

AC:

2034

AN:

53370

Middle Eastern (MID)

AF:

0.0765

AC:

336

AN:

4390

European-Non Finnish (NFE)

AF:

0.0346

AC:

38284

AN:

1106222

Other (OTH)

AF:

0.0542

AC:

3248

AN:

59958

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.476

Heterozygous variant carriers

2541

5082

7624

10165

12706

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1500

3000

4500

6000

7500

<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:

0.0379

AC:

5777

AN:

152294

Hom.:

229

Cov.:

AF XY:

0.0402

AC XY:

2990

AN XY:

74456

show subpopulations

African (AFR)

AF:

0.00796

AC:

331

AN:

41572

American (AMR)

AF:

0.0440

AC:

674

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.0743

AC:

258

AN:

3472

East Asian (EAS)

AF:

0.226

AC:

1170

AN:

5176

South Asian (SAS)

AF:

0.0653

AC:

315

AN:

4826

European-Finnish (FIN)

AF:

0.0372

AC:

395

AN:

10608

Middle Eastern (MID)

AF:

0.0952

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0369

AC:

2512

AN:

68018

Other (OTH)

AF:

0.0388

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

272

544

817

1089

1361

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

216

288

360

<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:

0.0401

Hom.:

Bravo

AF:

0.0378

Asia WGS

AF:

0.152

AC:

527

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.68

CADD

Benign

5.6

(source)

DANN

Benign

0.66

PhyloP100

-0.29

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over