dbSNP rs10770042: WEE1:p.Glu476Glu (chr11-9585485-A-G) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP7BA1

The NM_003390.4(WEE1):c.1428A>G(p.Glu476Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,599,370 control chromosomes in the GnomAD database, including 20,584 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 ( 1796 hom., cov: 32)

Exomes 𝑓: 0.16 ( 18788 hom. )

Consequence

WEE1
NM_003390.4 synonymous

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.33

Publications

26 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.55).

BP7

Synonymous conserved (PhyloP=1.33 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
WEE1	NM_003390.4 link	c.1428A>G	p.Glu476Glu	synonymous_variant	Exon 8 of 11	ENST00000450114.7	NP_003381.1
WEE1	NM_001143976.2 link	c.786A>G	p.Glu262Glu	synonymous_variant	Exon 8 of 11		NP_001137448.1
WEE1	XM_047427539.1 link	c.786A>G	p.Glu262Glu	synonymous_variant	Exon 8 of 11		XP_047283495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WEE1	ENST00000450114.7 link	c.1428A>G	p.Glu476Glu	synonymous_variant	Exon 8 of 11	1	NM_003390.4	ENSP00000402084.2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23375

AN:

152078

Hom.:

1792

Cov.:

show subpopulations

Gnomad AFR

AF:

0.128

Gnomad AMI

AF:

0.232

Gnomad AMR

AF:

0.172

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.209

Gnomad SAS

AF:

0.130

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.129

GnomAD2 exomes

AF:

0.149

AC:

35317

AN:

237388

AF XY:

0.148

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.132

Gnomad ASJ exome

AF:

0.109

Gnomad EAS exome

AF:

0.186

Gnomad FIN exome

AF:

0.186

Gnomad NFE exome

AF:

0.152

Gnomad OTH exome

AF:

0.145

GnomAD4 exome

AF:

0.158

AC:

229154

AN:

1447174

Hom.:

18788

Cov.:

AF XY:

0.157

AC XY:

113183

AN XY:

719656

show subpopulations

African (AFR)

AF:

0.124

AC:

4048

AN:

32522

American (AMR)

AF:

0.135

AC:

5435

AN:

40146

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

2891

AN:

25448

East Asian (EAS)

AF:

0.237

AC:

9359

AN:

39530

South Asian (SAS)

AF:

0.131

AC:

10812

AN:

82762

European-Finnish (FIN)

AF:

0.186

AC:

9889

AN:

53236

Middle Eastern (MID)

AF:

0.123

AC:

696

AN:

5680

European-Non Finnish (NFE)

AF:

0.160

AC:

176779

AN:

1108092

Other (OTH)

AF:

0.155

AC:

9245

AN:

59758

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.466

Heterozygous variant carriers

9243

18486

27729

36972

46215

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

6368

12736

19104

25472

31840

<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:

0.154

AC:

23384

AN:

152196

Hom.:

1796

Cov.:

AF XY:

0.157

AC XY:

11678

AN XY:

74406

show subpopulations

African (AFR)

AF:

0.128

AC:

5320

AN:

41538

American (AMR)

AF:

0.172

AC:

2627

AN:

15286

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

396

AN:

3472

East Asian (EAS)

AF:

0.209

AC:

1084

AN:

5176

South Asian (SAS)

AF:

0.131

AC:

630

AN:

4822

European-Finnish (FIN)

AF:

0.188

AC:

1982

AN:

10566

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10830

AN:

68024

Other (OTH)

AF:

0.127

AC:

268

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1010

2021

3031

4042

5052

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

264

528

792

1056

1320

<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:

0.152

Hom.:

7910

Bravo

AF:

0.148

Asia WGS

AF:

0.159

AC:

550

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.55

CADD

Benign

(source)

DANN

Benign

0.70

PhyloP100

1.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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