7-141719205-T-C

Position:

• chr7-141719205-T-C

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The ENST00000397541.6(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 ENST00000397541.6 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.57

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

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WEE2	NM_001105558.1	c.719T>C	p.Ile240Thr	missense_variant	4/12	ENST00000397541.6	NP_001099028.1
WEE2-AS1	NR_015392.1	n.656+4711A>G		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WEE2	ENST00000397541.6	c.719T>C	p.Ile240Thr	missense_variant	4/12	1	NM_001105558.1	ENSP00000380675	P1
WEE2-AS1	ENST00000665340.1	n.617+4711A>G		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

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

Aug 10, 2021

The c.719T>C (p.I240T) alteration is located in exon 4 (coding exon 4) of the WEE2 gene. This alteration results from a T to C substitution at nucleotide position 719, causing the isoleucine (I) at amino acid position 240 to be replaced by a threonine (T). 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	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;D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Pathogenic	3.3	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Benign	0.44	T
PROVEAN	Pathogenic	-4.6	D;D
REVEL	Pathogenic	0.73
Sift	Uncertain	0.0010	D;D
Sift4G	Uncertain	0.0020	D;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
Varity_R		0.86
gMVP		0.81

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-141419005;