Variant 11-9574165-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 2P and 6B. PM1BP4_ModerateBS2

The NM_003390.4(WEE1):c.232T>G(p.Ser78Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000583 in 1,029,240 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000058 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

WEE1
NM_003390.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.194

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 Likely_benign. Variant got -4 ACMG points.

PM1

In a modified_residue Phosphoserine (size 0) in uniprot entity WEE1_HUMAN

BP4

Computational evidence support a benign effect (MetaRNN=0.09193739).

BS2

High AC in GnomAdExome4 at 6 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4 linkuse as main transcript	c.232T>G	p.Ser78Ala	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.232T>G	p.Ser78Ala	missense_variant	1/11	1	NM_003390.4	P3	P30291-1
WEE1	ENST00000680141.1 linkuse as main transcript	c.232T>G	p.Ser78Ala	missense_variant, NMD_transcript_variant	1/12

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

147804

Hom.:

Cov.:

FAILED QC

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000583

AC:

AN:

1029240

Hom.:

Cov.:

AF XY:

0.00000206

AC XY:

AN XY:

486204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000477

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000104

Gnomad4 NFE exome

AF:

0.00000338

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

147920

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

72220

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:

0.00

Gnomad4 OTH

AF:

0.00

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

Nov 03, 2022

The c.232T>G (p.S78A) alteration is located in exon 1 (coding exon 1) of the WEE1 gene. This alteration results from a T to G substitution at nucleotide position 232, causing the serine (S) at amino acid position 78 to be replaced by an alanine (A). 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

0.065

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.089

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.26

FATHMM_MKL

Benign

0.56

LIST_S2

Benign

0.29

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.092

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

MutationTaster

Benign

0.84

PrimateAI

Pathogenic

0.89

PROVEAN

Benign

-0.61

REVEL

Benign

0.048

Sift

Benign

0.038

Sift4G

Benign

0.23

Polyphen

0.0

Vest4

0.079

MutPred

0.30

Loss of phosphorylation at S78 (P = 0);

MVP

0.11

MPC

1.1

ClinPred

0.12

GERP RS

2.8

Varity_R

0.12

gMVP

0.040

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over