11-9585485-A-G

Position:

• chr11-9585485-A-G

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_003390.4(WEE1):​c.1428A>G​(p.Glu476Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.158 in 1,599,370 control chromosomes in the GnomAD database, including 20,584 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 (1796 hom., cov: 32)
  • Exomes 𝑓: 0.16 (18788 hom.)
• Consequence: WEE1 NM_003390.4 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.33

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]

WEE1 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=1.33 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.199 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WEE1	NM_003390.4	c.1428A>G	p.Glu476Glu	synonymous_variant	8/11	ENST00000450114.7	NP_003381.1
WEE1	NM_001143976.2	c.786A>G	p.Glu262Glu	synonymous_variant	8/11		NP_001137448.1
WEE1	XM_047427539.1	c.786A>G	p.Glu262Glu	synonymous_variant	8/11		XP_047283495.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WEE1	ENST00000450114.7	c.1428A>G	p.Glu476Glu	synonymous_variant	8/11	1	NM_003390.4	ENSP00000402084.2

Frequencies

GnomAD3 genomes AF: 0.154 AC: 23375 AN: 152078 Hom.: 1792 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: 0.209

Gnomad SAS AF: 0.130

Gnomad FIN AF: 0.188

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.159

Gnomad OTH AF: 0.129

GnomAD3 exomes AF: 0.149 AC: 35317 AN: 237388 Hom.: 2759 AF XY: 0.148 AC XY: 18992 AN XY: 128310

Gnomad AFR exome AF: 0.126

Gnomad AMR exome AF: 0.132

Gnomad ASJ exome AF: 0.109

Gnomad EAS exome AF: 0.186

Gnomad SAS exome AF: 0.130

Gnomad FIN exome AF: 0.186

Gnomad NFE exome AF: 0.152

Gnomad OTH exome AF: 0.145

GnomAD4 exome AF: 0.158 AC: 229154 AN: 1447174 Hom.: 18788 Cov.: 32 AF XY: 0.157 AC XY: 113183 AN XY: 719656

Gnomad4 AFR exome AF: 0.124

Gnomad4 AMR exome AF: 0.135

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.237

Gnomad4 SAS exome AF: 0.131

Gnomad4 FIN exome AF: 0.186

Gnomad4 NFE exome AF: 0.160

Gnomad4 OTH exome AF: 0.155

GnomAD4 genome AF: 0.154 AC: 23384 AN: 152196 Hom.: 1796 Cov.: 32 AF XY: 0.157 AC XY: 11678 AN XY: 74406

Gnomad4 AFR AF: 0.128

Gnomad4 AMR AF: 0.172

Gnomad4 ASJ AF: 0.114

Gnomad4 EAS AF: 0.209

Gnomad4 SAS AF: 0.131

Gnomad4 FIN AF: 0.188

Gnomad4 NFE AF: 0.159

Gnomad4 OTH AF: 0.127

Alfa AF: 0.151 Hom.: 3946

Bravo AF: 0.148

Asia WGS AF: 0.159 AC: 550 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	13
DANN	Benign	0.70

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10770042; hg19: chr11-9607032; COSMIC: COSV55197239; COSMIC: COSV55197239;