7-141719205-T-C

Variant names:

• chr7-141719205-T-C
• rs1798860351
• NM_001105558.1:c.719T>C

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_001105558.1(WEE2):​c.719T>C​(p.Ile240Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: WEE2 NM_001105558.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57
• 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: Likely_pathogenic. The variant received 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.952

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.719T>C	p.Ile240Thr	missense	Exon 4 of 12	NP_001099028.1	P0C1S8
	WEE2-AS1	NR_015392.1		n.656+4711A>G		intron	N/A
	WEE2-AS1	NR_199840.1		n.923+4711A>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.719T>C	p.Ile240Thr	missense	Exon 4 of 12	ENSP00000380675.2	P0C1S8
	WEE2-AS1	ENST00000462383.6	TSL:1	n.412+4711A>G		intron	N/A
	WEE2-AS1	ENST00000465110.5	TSL:1	n.132+4711A>G		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.34	D
BayesDel_noAF	Pathogenic	0.26
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T
Eigen	Pathogenic	0.96
Eigen_PC	Pathogenic	0.87
FATHMM_MKL	Pathogenic	0.98	D
M_CAP	Benign	0.080	D
MetaRNN	Pathogenic	0.95	D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.3	M
PhyloP100		7.6
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.6	D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D
Sift4G	Uncertain	0.0020	D
Polyphen		0.99	D
Vest4		0.86
MutPred		0.83		Loss of stability (P = 0.0012)
MVP		0.88
MPC		0.69
ClinPred		1.0	D
GERP RS		5.5
PromoterAI		0.025	Neutral
Varity_R		0.86
gMVP		0.81
Mutation Taster		=27/73	disease causing

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: rs1798860351; hg19: chr7-141419005;