Variant 7-141719211-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001105558.1(WEE2):c.725G>A(p.Arg242His) variant causes a missense change. The variant allele was found at a frequency of 0.0000323 in 1,611,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R242C) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000033 ( 0 hom. )

Consequence

WEE2
NM_001105558.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.46

Variant links:

Genes affected

WEE2 (HGNC:19684): (WEE2 oocyte meiosis inhibiting kinase) Predicted to enable protein tyrosine kinase activity. Predicted to be involved in several processes, including female pronucleus assembly; negative regulation of oocyte maturation; and regulation of meiosis I. Located in cytosol; nucleoplasm; and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

WEE2 links:

WEE2-AS1 (HGNC:48669): (WEE2 antisense RNA 1)

WEE2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.37801754).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE2	NM_001105558.1 linkuse as main transcript	c.725G>A	p.Arg242His	missense_variant	4/12	ENST00000397541.6
WEE2-AS1	NR_015392.1 linkuse as main transcript	n.656+4705C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE2	ENST00000397541.6 linkuse as main transcript	c.725G>A	p.Arg242His	missense_variant	4/12	1	NM_001105558.1	P1
WEE2-AS1	ENST00000665340.1 linkuse as main transcript	n.617+4705C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000724

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000485

AC:

AN:

247276

Hom.:

AF XY:

0.0000447

AC XY:

AN XY:

134220

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000885

Gnomad ASJ exome

AF:

0.000402

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000332

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000355

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000329

AC:

AN:

1458992

Hom.:

Cov.:

AF XY:

0.0000262

AC XY:

AN XY:

725694

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000676

Gnomad4 ASJ exome

AF:

0.000269

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000351

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000279

Gnomad4 OTH exome

AF:

0.0000664

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152158

Hom.:

Cov.:

AF XY:

0.0000538

AC XY:

AN XY:

74336

show subpopulations

Gnomad4 AFR

AF:

0.0000724

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:

0.0000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000517

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000248

AC:

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 10, 2021

The c.725G>A (p.R242H) alteration is located in exon 4 (coding exon 4) of the WEE2 gene. This alteration results from a G to A substitution at nucleotide position 725, causing the arginine (R) at amino acid position 242 to be replaced by a histidine (H). 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

0.081

BayesDel_addAF

Benign

-0.044

BayesDel_noAF

Benign

-0.10

Cadd

Benign

Dann

Uncertain

1.0

DEOGEN2

Benign

0.19

T;.

Eigen

Uncertain

0.20

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Pathogenic

0.97

M_CAP

Benign

0.053

MetaRNN

Benign

0.38

T;T

MetaSVM

Benign

-0.48

MutationAssessor

Uncertain

2.7

M;.

MutationTaster

Benign

1.0

PrimateAI

Benign

0.34

PROVEAN

Uncertain

-3.7

D;D

REVEL

Benign

0.27

Sift

Benign

0.053

T;T

Sift4G

Uncertain

0.0040

D;T

Polyphen

0.22

B;.

Vest4

0.38

MVP

0.42

MPC

0.37

ClinPred

0.52

GERP RS

4.6

Varity_R

0.26

gMVP

0.68

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