rs11042431

chr11-9585129-A-Gchr11-9585129-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_003390.4(WEE1):c.1289-129A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 734,756 control chromosomes in the GnomAD database, including 9,550 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.15 (1794 hom., cov: 32)
  • Exomes 𝑓: 0.16 (7756 hom.)
• Consequence: WEE1 NM_003390.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.105

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.198 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE1	NM_003390.4	c.1289-129A>G		intron_variant		ENST00000450114.7
WEE1	NM_001143976.2	c.647-129A>G		intron_variant
WEE1	XM_047427539.1	c.647-129A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE1	ENST00000450114.7	c.1289-129A>G		intron_variant		1	NM_003390.4	P3

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23370 AN: 151984 Hom.: 1790 Cov.: 32

Gnomad AFR AF: 0.128

Gnomad AMI AF: 0.232

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.114

Gnomad EAS AF: 0.208

Gnomad SAS AF: 0.129

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.129

GnomAD4 exome AF: 0.160 AC: 93061 AN: 582654 Hom.: 7756 AF XY: 0.158 AC XY: 48359 AN XY: 306376

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.143

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.243

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.184

Gnomad4 NFE exome AF: 0.158

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.154 AC: 23379 AN: 152102 Hom.: 1794 Cov.: 32 AF XY: 0.157 AC XY: 11688 AN XY: 74352

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.208

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.128

Alfa AF: 0.0888 Hom.: 154

Bravo AF: 0.148

Asia WGS AF: 0.159 AC: 551 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	4.8
Dann	Benign	0.53
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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: rs11042431; hg19: chr11-9606676;