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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003390.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WEE1	NM_003390.4	MANE Select	c.1288+11C>T		intron	N/A	NP_003381.1	P30291-1
	WEE1	NM_001143976.2		c.646+11C>T		intron	N/A	NP_001137448.1	P30291-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WEE1	ENST00000450114.7	TSL:1 MANE Select	c.1288+11C>T	intron	N/A	ENSP00000402084.2	P30291-1
WEE1	ENST00000919884.1		c.1288+11C>T	intron	N/A	ENSP00000589943.1
WEE1	ENST00000919883.1		c.1288+11C>T	intron	N/A	ENSP00000589942.1

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 v4.9

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over