Variant chr11-9574508-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_003390.4(WEE1):c.575A>G(p.Lys192Arg) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000000941 in 1,062,398 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

WEE1
NM_003390.4 missense, splice_region

Scores

Splicing: ADA: 0.9978

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.11

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 Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4 linkuse as main transcript	c.575A>G	p.Lys192Arg	missense_variant, splice_region_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.575A>G	p.Lys192Arg	missense_variant, splice_region_variant	1/11	1	NM_003390.4	P3	P30291-1
WEE1	ENST00000680141.1 linkuse as main transcript	c.575A>G	p.Lys192Arg	missense_variant, splice_region_variant, NMD_transcript_variant	1/12

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.41e-7

AC:

AN:

1062398

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

510520

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000110

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

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

Sep 15, 2021

The c.575A>G (p.K192R) alteration is located in exon 1 (coding exon 1) of the WEE1 gene. This alteration results from a A to G substitution at nucleotide position 575, causing the lysine (K) at amino acid position 192 to be replaced by an arginine (R). 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

0.16

BayesDel_addAF

Benign

-0.092

BayesDel_noAF

Benign

-0.37

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Benign

0.41

Eigen

Uncertain

0.22

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.95

M_CAP

Uncertain

0.27

MetaRNN

Benign

0.22

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.16

Sift

Uncertain

0.017

Sift4G

Uncertain

0.038

Polyphen

0.56

Vest4

0.21

MutPred

0.17

Loss of ubiquitination at K192 (P = 0.0081);

MVP

0.24

MPC

1.2

ClinPred

0.97

GERP RS

4.3

Varity_R

0.38

gMVP

0.47

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

1.0

dbscSNV1_RF

Pathogenic

0.95

SpliceAI score (max)

0.080

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