Genetic Variant WEE1:c.*656A>G (chr11-9589258-A-G) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_003390.4(WEE1):c.*656A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 983,994 control chromosomes in the GnomAD database, including 12,412 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 0.15 ( 1664 hom., cov: 31)

Exomes 𝑓: 0.16 ( 10748 hom. )

Consequence

WEE1
NM_003390.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.34).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.196 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.*656A>G		3_prime_UTR	Exon 11 of 11	NP_003381.1	P30291-1
	WEE1	NM_001143976.2		c.*656A>G		3_prime_UTR	Exon 11 of 11	NP_001137448.1	P30291-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WEE1	ENST00000450114.7	TSL:1 MANE Select	c.*656A>G	3_prime_UTR	Exon 11 of 11	ENSP00000402084.2	P30291-1
WEE1	ENST00000919884.1		c.*656A>G	3_prime_UTR	Exon 12 of 12	ENSP00000589943.1
WEE1	ENST00000919883.1		c.*656A>G	3_prime_UTR	Exon 11 of 11	ENSP00000589942.1

Frequencies

GnomAD3 genomes

AF:

0.148

AC:

22245

AN:

150696

Hom.:

1661

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.234

Gnomad AMR

AF:

0.170

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.206

Gnomad SAS

AF:

0.128

Gnomad FIN

AF:

0.192

Gnomad MID

AF:

0.133

Gnomad NFE

AF:

0.160

Gnomad OTH

AF:

0.126

GnomAD4 exome

AF:

0.160

AC:

133147

AN:

833190

Hom.:

10748

Cov.:

AF XY:

0.160

AC XY:

61484

AN XY:

384850

show subpopulations

African (AFR)

AF:

0.0943

AC:

1487

AN:

15776

American (AMR)

AF:

0.153

AC:

151

AN:

984

Ashkenazi Jewish (ASJ)

AF:

0.120

AC:

618

AN:

5148

East Asian (EAS)

AF:

0.202

AC:

733

AN:

3626

South Asian (SAS)

AF:

0.127

AC:

2090

AN:

16450

European-Finnish (FIN)

AF:

0.194

AC:

134

AN:

692

Middle Eastern (MID)

AF:

0.119

AC:

192

AN:

1620

European-Non Finnish (NFE)

AF:

0.162

AC:

123491

AN:

761600

Other (OTH)

AF:

0.156

AC:

4251

AN:

27294

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.477

Heterozygous variant carriers

5442

10884

16325

21767

27209

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5976

11952

17928

23904

29880

<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:

0.148

AC:

22250

AN:

150804

Hom.:

1664

Cov.:

AF XY:

0.151

AC XY:

11110

AN XY:

73598

show subpopulations

African (AFR)

AF:

0.105

AC:

4358

AN:

41332

American (AMR)

AF:

0.171

AC:

2577

AN:

15098

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

394

AN:

3460

East Asian (EAS)

AF:

0.206

AC:

1061

AN:

5154

South Asian (SAS)

AF:

0.129

AC:

619

AN:

4792

European-Finnish (FIN)

AF:

0.192

AC:

1945

AN:

10130

Middle Eastern (MID)

AF:

0.129

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.160

AC:

10785

AN:

67546

Other (OTH)

AF:

0.125

AC:

262

AN:

2098

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

974

1948

2922

3896

4870

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

252

504

756

1008

1260

<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:

0.150

Hom.:

2050

Bravo

AF:

0.140

Asia WGS

AF:

0.153

AC:

529

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.34

CADD

Benign

(source)

DANN

Benign

0.88

PhyloP100

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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