7-141708827-G-C

Position:

chr7-141708827-G-C

Variant summary

Our verdict is Likely benign. Variant got -3 ACMG points: 2P and 5B. PM2BP4_StrongBS1_Supporting

The ENST00000397541.6(WEE2):c.69G>C(p.Glu23Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000892 in 1,614,166 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00051 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000046 ( 0 hom. )

Consequence

WEE2
ENST00000397541.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.715

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 Likely_benign. Variant got -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.010562003).

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000506 (77/152288) while in subpopulation AFR AF= 0.00178 (74/41556). AF 95% confidence interval is 0.00145. There are 0 homozygotes in gnomad4. There are 32 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck. Existence of Clinvar submissions makes me limit the strength of this signal to Supporting

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WEE2	NM_001105558.1 linkuse as main transcript	c.69G>C	p.Glu23Asp	missense_variant	1/12	ENST00000397541.6	NP_001099028.1
WEE2-AS1	NR_015392.1 linkuse as main transcript	n.843-3070C>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WEE2	ENST00000397541.6 linkuse as main transcript	c.69G>C	p.Glu23Asp	missense_variant	1/12	1	NM_001105558.1	ENSP00000380675	P1
WEE2-AS1	ENST00000665340.1 linkuse as main transcript	n.618-3070C>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.000493

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00174

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

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:

0.0000294

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000721

AC:

AN:

249486

Hom.:

AF XY:

0.0000739

AC XY:

AN XY:

135358

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000458

AC:

AN:

1461878

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00167

Gnomad4 AMR exome

AF:

0.0000447

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.000132

GnomAD4 genome

AF:

0.000506

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000430

AC XY:

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00178

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000294

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000163

Hom.:

Bravo

AF:

0.000552

ESP6500AA

AF:

0.00210

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000579

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

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

Jul 26, 2022

The c.69G>C (p.E23D) alteration is located in exon 1 (coding exon 1) of the WEE2 gene. This alteration results from a G to C substitution at nucleotide position 69, causing the glutamic acid (E) at amino acid position 23 to be replaced by an aspartic acid (D). 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

0.082

BayesDel_addAF

Benign

-0.59

BayesDel_noAF

Benign

-0.64

CADD

Benign

DANN

Benign

0.97

DEOGEN2

Benign

0.018

Eigen

Benign

-0.39

Eigen_PC

Benign

-0.46

FATHMM_MKL

Benign

0.54

M_CAP

Benign

0.0031

MetaRNN

Benign

0.011

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.5

MutationTaster

Benign

1.0

PrimateAI

Benign

0.35

PROVEAN

Benign

-0.23

REVEL

Benign

0.066

Sift

Benign

0.31

Sift4G

Benign

0.47

Polyphen

0.61

Vest4

0.22

MutPred

0.22

Gain of phosphorylation at T22 (P = 0.1769);

MVP

0.13

MPC

0.46

ClinPred

0.021

GERP RS

2.9

Varity_R

0.069

gMVP

0.0086

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