Variant 11-9575939-G-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003390.4(WEE1):c.628G>T(p.Gly210Cys) variant causes a missense change. The variant allele was found at a frequency of 0.00703 in 1,614,084 control chromosomes in the GnomAD database, including 63 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0057 ( 4 hom., cov: 32)

Exomes 𝑓: 0.0072 ( 59 hom. )

Consequence

WEE1
NM_003390.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 4.02

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0043308735).

BP6

Variant 11-9575939-G-T is Benign according to our data. Variant chr11-9575939-G-T is described in ClinVar as [Benign]. Clinvar id is 789442.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High AC in GnomAd4 at 869 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
WEE1	NM_003390.4 linkuse as main transcript	c.628G>T	p.Gly210Cys	missense_variant	2/11	ENST00000450114.7
WEE1	NM_001143976.2 linkuse as main transcript	c.-15G>T		5_prime_UTR_variant	2/11
WEE1	XM_047427539.1 linkuse as main transcript	c.-15G>T		5_prime_UTR_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE1	ENST00000450114.7 linkuse as main transcript	c.628G>T	p.Gly210Cys	missense_variant	2/11	1	NM_003390.4	P3	P30291-1

Frequencies

GnomAD3 genomes

AF:

0.00571

AC:

868

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00116

Gnomad AMI

AF:

0.0231

Gnomad AMR

AF:

0.00327

Gnomad ASJ

AF:

0.0164

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.0116

Gnomad FIN

AF:

0.00633

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.00816

Gnomad OTH

AF:

0.00525

GnomAD3 exomes

AF:

0.00731

AC:

1839

AN:

251442

Hom.:

AF XY:

0.00798

AC XY:

1084

AN XY:

135900

show subpopulations

Gnomad AFR exome

AF:

0.00111

Gnomad AMR exome

AF:

0.00402

Gnomad ASJ exome

AF:

0.0137

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0143

Gnomad FIN exome

AF:

0.00711

Gnomad NFE exome

AF:

0.00805

Gnomad OTH exome

AF:

0.00587

GnomAD4 exome

AF:

0.00717

AC:

10480

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00747

AC XY:

5429

AN XY:

727214

show subpopulations

Gnomad4 AFR exome

AF:

0.00114

Gnomad4 AMR exome

AF:

0.00427

Gnomad4 ASJ exome

AF:

0.0130

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0143

Gnomad4 FIN exome

AF:

0.00644

Gnomad4 NFE exome

AF:

0.00705

Gnomad4 OTH exome

AF:

0.00685

GnomAD4 genome

AF:

0.00571

AC:

869

AN:

152248

Hom.:

Cov.:

AF XY:

0.00550

AC XY:

409

AN XY:

74430

show subpopulations

Gnomad4 AFR

AF:

0.00116

Gnomad4 AMR

AF:

0.00327

Gnomad4 ASJ

AF:

0.0164

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.0116

Gnomad4 FIN

AF:

0.00633

Gnomad4 NFE

AF:

0.00817

Gnomad4 OTH

AF:

0.00520

Alfa

AF:

0.00633

Hom.:

Bravo

AF:

0.00577

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000909

AC:

ESP6500EA

AF:

0.00955

AC:

ExAC

AF:

0.00703

AC:

854

Asia WGS

AF:

0.00318

AC:

AN:

3478

EpiCase

AF:

0.00905

EpiControl

AF:

0.00830

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jun 19, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.40

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.084

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.20

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.75

MetaRNN

Benign

0.0043

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.8

MutationTaster

Benign

0.99

D;D

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-1.1

REVEL

Benign

0.078

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.90

Vest4

0.36

MVP

0.068

MPC

2.1

ClinPred

0.037

GERP RS

3.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.22

gMVP

0.23

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

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