Variant chr11-9574063-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_003390.4(WEE1):c.130G>A(p.Gly44Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000689 in 1,247,920 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000074 ( 0 hom. )

Consequence

WEE1
NM_003390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.81

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 made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12099928).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4 linkuse as main transcript	c.130G>A	p.Gly44Ser	missense_variant	1/11	ENST00000450114.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE1	ENST00000450114.7 linkuse as main transcript	c.130G>A	p.Gly44Ser	missense_variant	1/11	1	NM_003390.4	P3	P30291-1
WEE1	ENST00000680141.1 linkuse as main transcript	c.130G>A	p.Gly44Ser	missense_variant, NMD_transcript_variant	1/12

Frequencies

GnomAD3 genomes

AF:

0.0000332

AC:

AN:

150436

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000741

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000240

AC:

AN:

4168

Hom.:

AF XY:

0.000455

AC XY:

AN XY:

2198

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000444

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000738

AC:

AN:

1097484

Hom.:

Cov.:

AF XY:

0.0000591

AC XY:

AN XY:

524522

show subpopulations

Gnomad4 AFR exome

AF:

0.0000441

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000861

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000332

AC:

AN:

150436

Hom.:

Cov.:

AF XY:

0.0000136

AC XY:

AN XY:

73426

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000741

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000142

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 14, 2022

The c.130G>A (p.G44S) alteration is located in exon 1 (coding exon 1) of the WEE1 gene. This alteration results from a G to A substitution at nucleotide position 130, causing the glycine (G) at amino acid position 44 to be replaced by a serine (S). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.052

Eigen

Benign

-0.58

Eigen_PC

Benign

-0.49

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.55

M_CAP

Pathogenic

0.75

MetaRNN

Benign

0.12

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.34

MutationTaster

Benign

0.81

PrimateAI

Pathogenic

0.83

PROVEAN

Benign

0.34

REVEL

Benign

0.20

Sift

Benign

0.23

Sift4G

Uncertain

0.059

Polyphen

0.090

Vest4

0.16

MutPred

0.22

Gain of phosphorylation at G44 (P = 5e-04);

MVP

0.43

MPC

2.4

ClinPred

0.15

GERP RS

2.6

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.089

gMVP

0.054

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over