dbSNP rs11042431: WEE1:c.1289-129A>G (chr11-9585129-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.1289-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 734,756 control chromosomes in the GnomAD database, including 9,550 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 ( 1794 hom., cov: 32)

Exomes 𝑓: 0.16 ( 7756 hom. )

Consequence

WEE1
NM_003390.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.105

Publications

1 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 -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 = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein
WEE1	NM_003390.4 link	c.1289-129A>G	intron_variant	Intron 6 of 10	ENST00000450114.7	NP_003381.1
WEE1	NM_001143976.2 link	c.647-129A>G	intron_variant	Intron 6 of 10		NP_001137448.1
WEE1	XM_047427539.1 link	c.647-129A>G	intron_variant	Intron 6 of 10		XP_047283495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WEE1	ENST00000450114.7 link	c.1289-129A>G		intron_variant	Intron 6 of 10	1	NM_003390.4	ENSP00000402084.2

Frequencies

GnomAD3 genomes

AF:

0.154

AC:

23370

AN:

151984

Hom.:

1790

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:

0.208

Gnomad SAS

AF:

0.129

Gnomad FIN

AF:

0.188

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.159

Gnomad OTH

AF:

0.129

GnomAD4 exome

AF:

0.160

AC:

93061

AN:

582654

Hom.:

7756

AF XY:

0.158

AC XY:

48359

AN XY:

306376

show subpopulations

African (AFR)

AF:

0.124

AC:

1842

AN:

14842

American (AMR)

AF:

0.143

AC:

2896

AN:

20206

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

1705

AN:

14998

East Asian (EAS)

AF:

0.243

AC:

8079

AN:

33250

South Asian (SAS)

AF:

0.131

AC:

6478

AN:

49536

European-Finnish (FIN)

AF:

0.184

AC:

7043

AN:

38230

Middle Eastern (MID)

AF:

0.131

AC:

290

AN:

2218

European-Non Finnish (NFE)

AF:

0.158

AC:

60052

AN:

379152

Other (OTH)

AF:

0.155

AC:

4676

AN:

30222

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

3733

7466

11200

14933

18666

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

1076

2152

3228

4304

5380

<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:

23379

AN:

152102

Hom.:

1794

Cov.:

AF XY:

0.157

AC XY:

11688

AN XY:

74352

show subpopulations

African (AFR)

AF:

0.128

AC:

5318

AN:

41516

American (AMR)

AF:

0.172

AC:

2623

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.114

AC:

396

AN:

3470

East Asian (EAS)

AF:

0.208

AC:

1077

AN:

5172

South Asian (SAS)

AF:

0.131

AC:

630

AN:

4824

European-Finnish (FIN)

AF:

0.188

AC:

1987

AN:

10562

Middle Eastern (MID)

AF:

0.119

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.159

AC:

10831

AN:

67984

Other (OTH)

AF:

0.128

AC:

270

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1021

2042

3062

4083

5104

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:

0.0905

Hom.:

160

Bravo

AF:

0.148

Asia WGS

AF:

0.159

AC:

551

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.8

(source)

DANN

Benign

0.53

PhyloP100

0.10

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)

0.0

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over