chr11-9574367-G-A

Position:

• chr11-9574367-G-A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_003390.4(WEE1):​c.434G>A​(p.Gly145Asp) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WEE1 NM_003390.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.13

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 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=0.054731607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4	c.434G>A	p.Gly145Asp	missense_variant	1/11	ENST00000450114.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE1	ENST00000450114.7	c.434G>A	p.Gly145Asp	missense_variant	1/11	1	NM_003390.4	P3
WEE1	ENST00000680141.1	c.434G>A	p.Gly145Asp	missense_variant, NMD_transcript_variant	1/12

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1083576 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 521006

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: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 31

ExAC AF: 0.00000980 AC: 1

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

Jul 14, 2021

The c.434G>A (p.G145D) alteration is located in exon 1 (coding exon 1) of the WEE1 gene. This alteration results from a G to A substitution at nucleotide position 434, causing the glycine (G) at amino acid position 145 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	0.092
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Benign	-0.38
CADD	Benign	17
DANN	Uncertain	0.97
DEOGEN2	Benign	0.064	T
Eigen	Benign	-0.21
Eigen_PC	Benign	-0.21
FATHMM_MKL	Benign	0.69	D
LIST_S2	Benign	0.51	T
M_CAP	Pathogenic	0.55	D
MetaRNN	Benign	0.055	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
MutationTaster	Benign	0.77	D
PrimateAI	Pathogenic	0.91	D
PROVEAN	Benign	-0.090	N
REVEL	Benign	0.090
Sift	Benign	0.086	T
Sift4G	Benign	0.55	T
Polyphen		0.60	P
Vest4		0.13
MutPred		0.17		Loss of methylation at R142 (P = 0.0544);
MVP		0.14
MPC		1.8
ClinPred		0.35	T
GERP RS		2.7
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		2.2
Varity_R		0.055
gMVP		0.14

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

Other links and lift over

dbSNP: rs749689471; hg19: chr11-9595914;