chr11-9575978-A-G

Position:

• chr11-9575978-A-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_003390.4(WEE1):​c.667A>G​(p.Arg223Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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)
• Consequence: WEE1 NM_003390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.04

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.082265854).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4	c.667A>G	p.Arg223Gly	missense_variant	2/11	ENST00000450114.7
WEE1	NM_001143976.2	c.25A>G	p.Arg9Gly	missense_variant	2/11
WEE1	XM_047427539.1	c.25A>G	p.Arg9Gly	missense_variant	2/11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE1	ENST00000450114.7	c.667A>G	p.Arg223Gly	missense_variant	2/11	1	NM_003390.4	P3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 05, 2021

The c.667A>G (p.R223G) alteration is located in exon 2 (coding exon 2) of the WEE1 gene. This alteration results from a A to G substitution at nucleotide position 667, causing the arginine (R) at amino acid position 223 to be replaced by a glycine (G). 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	0.069
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.40
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.059	T;.
Eigen	Benign	-0.29
Eigen_PC	Benign	-0.12
FATHMM_MKL	Uncertain	0.82	D
LIST_S2	Benign	0.67	T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.082	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.34	N;.
MutationTaster	Benign	0.53	D;N
PrimateAI	Benign	0.33	T
PROVEAN	Benign	-0.26	N;N
REVEL	Benign	0.023
Sift	Benign	0.41	T;D
Sift4G	Benign	0.40	T;T
Polyphen		0.0010	B;.
Vest4		0.21
MutPred		0.30		Gain of relative solvent accessibility (P = 0.0479);.;
MVP		0.20
MPC		1.6
ClinPred		0.52	D
GERP RS		3.3
Varity_R		0.13
gMVP		0.25

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-9597525;