Genetic Variant WEE1:c.1141+1133A>G (chr11-9578396-A-G) – 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.1141+1133A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.446 in 154,426 control chromosomes in the GnomAD database, including 15,752 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 0.45 ( 15485 hom., cov: 33)

Exomes 𝑓: 0.46 ( 267 hom. )

Consequence

WEE1
NM_003390.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.967

Publications

11 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=-0.86).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.6 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.1141+1133A>G		intron	N/A	NP_003381.1	P30291-1
	WEE1	NM_001143976.2		c.499+1133A>G		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.1141+1133A>G	intron	N/A	ENSP00000402084.2	P30291-1
WEE1	ENST00000919884.1		c.1141+1133A>G	intron	N/A	ENSP00000589943.1
WEE1	ENST00000919883.1		c.1141+1133A>G	intron	N/A	ENSP00000589942.1

Frequencies

GnomAD3 genomes

AF:

0.446

AC:

67806

AN:

151894

Hom.:

15479

Cov.:

show subpopulations

Gnomad AFR

AF:

0.475

Gnomad AMI

AF:

0.402

Gnomad AMR

AF:

0.507

Gnomad ASJ

AF:

0.458

Gnomad EAS

AF:

0.618

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.413

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.409

Gnomad OTH

AF:

0.499

GnomAD4 exome

AF:

0.460

AC:

1111

AN:

2414

Hom.:

267

Cov.:

AF XY:

0.464

AC XY:

582

AN XY:

1254

show subpopulations

African (AFR)

AF:

0.500

AC:

AN:

American (AMR)

AF:

0.639

AC:

AN:

122

Ashkenazi Jewish (ASJ)

AF:

0.500

AC:

AN:

East Asian (EAS)

AF:

0.650

AC:

AN:

South Asian (SAS)

AF:

0.419

AC:

AN:

172

European-Finnish (FIN)

AF:

0.500

AC:

AN:

130

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.440

AC:

765

AN:

1740

Other (OTH)

AF:

0.500

AC:

AN:

162

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

128

160

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<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:

0.446

AC:

67840

AN:

152012

Hom.:

15485

Cov.:

AF XY:

0.445

AC XY:

33077

AN XY:

74294

show subpopulations

African (AFR)

AF:

0.475

AC:

19682

AN:

41446

American (AMR)

AF:

0.507

AC:

7741

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.458

AC:

1587

AN:

3468

East Asian (EAS)

AF:

0.618

AC:

3200

AN:

5178

South Asian (SAS)

AF:

0.392

AC:

1894

AN:

4828

European-Finnish (FIN)

AF:

0.413

AC:

4364

AN:

10560

Middle Eastern (MID)

AF:

0.571

AC:

168

AN:

294

European-Non Finnish (NFE)

AF:

0.409

AC:

27785

AN:

67952

Other (OTH)

AF:

0.500

AC:

1054

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1908

3816

5724

7632

9540

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

630

1260

1890

2520

3150

<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:

0.435

Hom.:

14393

Bravo

AF:

0.462

Asia WGS

AF:

0.510

AC:

1768

AN:

3472

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.94

(source)

DANN

Benign

0.70

PhyloP100

-0.97

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over