Genetic Variant NM_003390.4:c.1428A>G (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

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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