Genetic Variant WEE1:c.1288+11C>T (chr11-9581689-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_003390.4(WEE1):c.1288+11C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.377 in 1,603,850 control chromosomes in the GnomAD database, including 116,168 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.40 ( 12630 hom., cov: 33)

Exomes 𝑓: 0.37 ( 103538 hom. )

Consequence

WEE1
NM_003390.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.81

Publications

15 publications found

Variant links:

Genes affected

WEE1 (HGNC:12761): (WEE1 G2 checkpoint kinase) This gene encodes a nuclear protein, which is a tyrosine kinase belonging to the Ser/Thr family of protein kinases. This protein catalyzes the inhibitory tyrosine phosphorylation of CDC2/cyclin B kinase, and appears to coordinate the transition between DNA replication and mitosis by protecting the nucleus from cytoplasmically activated CDC2 kinase. [provided by RefSeq, Jul 2008]

WEE1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.75).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.445 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
WEE1	NM_003390.4 link	c.1288+11C>T	intron_variant	Intron 6 of 10	ENST00000450114.7	NP_003381.1	P30291-1Q86V29
WEE1	NM_001143976.2 link	c.646+11C>T	intron_variant	Intron 6 of 10		NP_001137448.1	P30291-2
WEE1	XM_047427539.1 link	c.646+11C>T	intron_variant	Intron 6 of 10		XP_047283495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WEE1	ENST00000450114.7 link	c.1288+11C>T		intron_variant	Intron 6 of 10	1	NM_003390.4	ENSP00000402084.2		P30291-1

Frequencies

GnomAD3 genomes

AF:

0.402

AC:

61088

AN:

151912

Hom.:

12625

Cov.:

show subpopulations

Gnomad AFR

AF:

0.451

Gnomad AMI

AF:

0.393

Gnomad AMR

AF:

0.453

Gnomad ASJ

AF:

0.426

Gnomad EAS

AF:

0.460

Gnomad SAS

AF:

0.376

Gnomad FIN

AF:

0.344

Gnomad MID

AF:

0.535

Gnomad NFE

AF:

0.364

Gnomad OTH

AF:

0.445

GnomAD2 exomes

AF:

0.408

AC:

99140

AN:

242772

AF XY:

0.402

show subpopulations

Gnomad AFR exome

AF:

0.448

Gnomad AMR exome

AF:

0.559

Gnomad ASJ exome

AF:

0.412

Gnomad EAS exome

AF:

0.457

Gnomad FIN exome

AF:

0.342

Gnomad NFE exome

AF:

0.372

Gnomad OTH exome

AF:

0.414

GnomAD4 exome

AF:

0.374

AC:

542981

AN:

1451820

Hom.:

103538

Cov.:

AF XY:

0.374

AC XY:

270119

AN XY:

722382

show subpopulations

African (AFR)

AF:

0.454

AC:

14949

AN:

32904

American (AMR)

AF:

0.546

AC:

22684

AN:

41570

Ashkenazi Jewish (ASJ)

AF:

0.412

AC:

10669

AN:

25870

East Asian (EAS)

AF:

0.470

AC:

18625

AN:

39586

South Asian (SAS)

AF:

0.383

AC:

32305

AN:

84440

European-Finnish (FIN)

AF:

0.338

AC:

17973

AN:

53184

Middle Eastern (MID)

AF:

0.528

AC:

3026

AN:

5726

European-Non Finnish (NFE)

AF:

0.361

AC:

399927

AN:

1108524

Other (OTH)

AF:

0.380

AC:

22823

AN:

60016

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.463

Heterozygous variant carriers

15473

30945

46418

61890

77363

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

12878

25756

38634

51512

64390

<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:

0.402

AC:

61119

AN:

152030

Hom.:

12630

Cov.:

AF XY:

0.400

AC XY:

29760

AN XY:

74324

show subpopulations

African (AFR)

AF:

0.451

AC:

18689

AN:

41462

American (AMR)

AF:

0.453

AC:

6923

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.426

AC:

1477

AN:

3464

East Asian (EAS)

AF:

0.460

AC:

2376

AN:

5170

South Asian (SAS)

AF:

0.375

AC:

1807

AN:

4816

European-Finnish (FIN)

AF:

0.344

AC:

3628

AN:

10550

Middle Eastern (MID)

AF:

0.527

AC:

155

AN:

294

European-Non Finnish (NFE)

AF:

0.364

AC:

24765

AN:

67976

Other (OTH)

AF:

0.447

AC:

941

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1865

3730

5595

7460

9325

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

582

1164

1746

2328

2910

<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:

0.391

Hom.:

21150

Bravo

AF:

0.419

Asia WGS

AF:

0.415

AC:

1441

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.75

CADD

Benign

3.0

(source)

DANN

Benign

0.76

PhyloP100

-1.8

PromoterAI

-0.0062

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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

Computational scores

Splicing

Publications

Other links and lift over