Variant chr7-141709045-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000397541.6(WEE2):c.287C>T(p.Ala96Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 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: not found (cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Consequence

WEE2
ENST00000397541.6 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.243

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:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.028404772).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WEE2	NM_001105558.1 linkuse as main transcript	c.287C>T	p.Ala96Val	missense_variant	1/12	ENST00000397541.6	NP_001099028.1
WEE2-AS1	NR_015392.1 linkuse as main transcript	n.843-3288G>A		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.287C>T	p.Ala96Val	missense_variant	1/12	1	NM_001105558.1	ENSP00000380675	P1
WEE2-AS1	ENST00000665340.1 linkuse as main transcript	n.618-3288G>A		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249100

Hom.:

AF XY:

0.00000740

AC XY:

AN XY:

135152

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

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:

0.00000886

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727234

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:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

ExAC

AF:

0.00000827

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

Jun 22, 2021

The c.287C>T (p.A96V) alteration is located in exon 1 (coding exon 1) of the WEE2 gene. This alteration results from a C to T substitution at nucleotide position 287, causing the alanine (A) at amino acid position 96 to be replaced by a valine (V). 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

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

7.5

DANN

Benign

0.50

DEOGEN2

Benign

0.022

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.011

M_CAP

Benign

0.0046

MetaRNN

Benign

0.028

MetaSVM

Benign

-0.97

MutationAssessor

Benign

1.4

MutationTaster

Benign

1.0

PrimateAI

Benign

0.23

PROVEAN

Benign

-0.11

REVEL

Benign

0.023

Sift

Benign

0.46

Sift4G

Benign

0.43

Polyphen

0.0090

Vest4

0.069

MutPred

0.078

Loss of glycosylation at P95 (P = 0.1204);

MVP

0.014

MPC

0.14

ClinPred

0.015

GERP RS

0.98

Varity_R

0.018

gMVP

0.061

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