chr7-141723982-G-A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001105558.1(WEE2):c.1069G>A(p.Gly357Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000614 in 1,612,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

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

Exomes 𝑓: 0.000065 ( 0 hom. )

Consequence

WEE2
NM_001105558.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 1.77

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.10707557).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WEE2	NM_001105558.1 link	c.1069G>A	p.Gly357Arg	missense_variant	Exon 7 of 12	ENST00000397541.6	NP_001099028.1	P0C1S8
WEE2-AS1	NR_015392.1 link	n.590C>T		non_coding_transcript_exon_variant	Exon 5 of 7
WEE2-AS1	NR_199840.1 link	n.857C>T		non_coding_transcript_exon_variant	Exon 3 of 5
WEE2-AS1	NR_199841.1 link	n.857C>T		non_coding_transcript_exon_variant	Exon 3 of 4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WEE2	ENST00000397541.6 link	c.1069G>A	p.Gly357Arg	missense_variant	Exon 7 of 12	1	NM_001105558.1	ENSP00000380675.2		P0C1S8

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

151960

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:

0.000386

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.0000806

AC:

AN:

248244

AF XY:

0.000126

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000175

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000709

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000650

AC:

AN:

1460604

Hom.:

Cov.:

AF XY:

0.0000908

AC XY:

AN XY:

726546

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33410

American (AMR)

AF:

0.000180

AC:

AN:

44538

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26104

East Asian (EAS)

AF:

0.00

AC:

AN:

39626

South Asian (SAS)

AF:

0.000233

AC:

AN:

85864

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53388

Middle Eastern (MID)

AF:

0.000347

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

0.0000531

AC:

AN:

1111568

Other (OTH)

AF:

0.0000994

AC:

AN:

60346

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152078

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74344

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41476

American (AMR)

AF:

0.00

AC:

AN:

15268

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.000387

AC:

AN:

5174

South Asian (SAS)

AF:

0.00

AC:

AN:

4816

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10572

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67992

Other (OTH)

AF:

0.000474

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000448

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.0000911

AC:

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 12, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.1069G>A (p.G357R) alteration is located in exon 7 (coding exon 7) of the WEE2 gene. This alteration results from a G to A substitution at nucleotide position 1069, causing the glycine (G) at amino acid position 357 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

not provided

Uncertain:1

May 01, 2021

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.097

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.35

CADD

Benign

(source)

DANN

Benign

0.82

DEOGEN2

Benign

0.034

T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.34

M_CAP

Benign

0.039

MetaRNN

Benign

0.11

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.3

L;.

PhyloP100

1.8

PrimateAI

Benign

0.24

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.22

Sift

Benign

0.57

T;T

Sift4G

Benign

0.53

T;T

Polyphen

0.071

B;.

Vest4

0.16

MutPred

0.41

Loss of catalytic residue at V358 (P = 0.061);.;

MVP

0.60

MPC

0.33

ClinPred

0.041

GERP RS

4.4

Varity_R

0.17

gMVP

0.55

Mutation Taster

=93/7

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over