7-141716226-G-C

Variant names:

• chr7-141716226-G-C
• rs1177880801
• NM_001105558.1:c.544G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001105558.1(WEE2):​c.544G>C​(p.Glu182Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000754 in 1,459,220 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000075 (0 hom.)
• Consequence: WEE2 NM_001105558.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.90
• Publications: 0 publications found

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-AS1 (HGNC:48669): (WEE2 antisense RNA 1)

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11531699).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001105558.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WEE2	NM_001105558.1	MANE Select	c.544G>C	p.Glu182Gln	missense	Exon 3 of 12	NP_001099028.1	P0C1S8
	WEE2-AS1	NR_015392.1		n.657-1852C>G		intron	N/A
	WEE2-AS1	NR_199840.1		n.924-1852C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WEE2	ENST00000397541.6	TSL:1 MANE Select	c.544G>C	p.Glu182Gln	missense	Exon 3 of 12	ENSP00000380675.2	P0C1S8
	WEE2-AS1	ENST00000462383.6	TSL:1	n.413-1852C>G		intron	N/A
	WEE2-AS1	ENST00000465110.5	TSL:1	n.132+7690C>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD2 exomes AF: 0.0000161 AC: 4 AN: 248158 AF XY: 0.0000148

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000291

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000177

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.00000754 AC: 11 AN: 1459220 Hom.: 0 Cov.: 31 AF XY: 0.00000689 AC XY: 5 AN XY: 725870

African (AFR) AF: 0.00 AC: 0 AN: 33298

American (AMR) AF: 0.0000673 AC: 3 AN: 44554

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26064

East Asian (EAS) AF: 0.00 AC: 0 AN: 39578

South Asian (SAS) AF: 0.00 AC: 0 AN: 85602

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53134

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5704

European-Non Finnish (NFE) AF: 0.00000720 AC: 8 AN: 1111026

Other (OTH) AF: 0.00 AC: 0 AN: 60260

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.050	T
Eigen	Benign	0.14
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.69	D
M_CAP	Benign	0.0039	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.9
PrimateAI	Benign	0.34	T
PROVEAN	Benign	-1.7	N
REVEL	Benign	0.059
Sift	Benign	0.25	T
Sift4G	Benign	0.10	T
Polyphen		0.79	P
Vest4		0.13
MutPred		0.16		Gain of MoRF binding (P = 0.0564)
MVP		0.33
MPC		0.22
ClinPred		0.54	D
GERP RS		3.5
Varity_R		0.12
gMVP		0.45
Mutation Taster		=93/7	polymorphism

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

Other links and lift over

dbSNP: rs1177880801; hg19: chr7-141416026;