rs1554415096

chr7-141719186-G-Achr7-141719186-G-Cchr7-141719186-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PM5

The NM_001105558.1(WEE2):c.700G>A(p.Asp234Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D234H) has been classified as Pathogenic.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WEE2 NM_001105558.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 9.46

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 Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PM5: Other missense variant is known to change same aminoacid residue: Variant chr7-141719186-G-C is described in ClinVar as [Pathogenic]. Clinvar id is 545469.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WEE2	NM_001105558.1	c.700G>A	p.Asp234Asn	missense_variant	4/12	ENST00000397541.6
WEE2-AS1	NR_015392.1	n.656+4730C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WEE2	ENST00000397541.6	c.700G>A	p.Asp234Asn	missense_variant	4/12	1	NM_001105558.1	P1
WEE2-AS1	ENST00000665340.1	n.617+4730C>T		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.80
BayesDel_addAF	Benign	-0.060	T
BayesDel_noAF	Benign	-0.32
Cadd	Pathogenic	28
Dann	Pathogenic	1.0
DEOGEN2	Benign	0.23	T;.
Eigen	Pathogenic	0.92
Eigen_PC	Pathogenic	0.89
FATHMM_MKL	Pathogenic	0.99	D
M_CAP	Benign	0.078	D
MetaRNN	Uncertain	0.68	D;D
MetaSVM	Uncertain	0.0090	D
MutationAssessor	Benign	2.0	M;.
MutationTaster	Benign	1.0	D
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.9	D;D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D;D
Sift4G	Pathogenic	0.0	D;D
Polyphen		1.0	D;.
Vest4		0.66
MutPred		0.65		Gain of MoRF binding (P = 0.0408);.;
MVP		0.72
MPC		0.62
ClinPred		1.0	D
GERP RS		5.5
Varity_R		0.86
gMVP		0.64

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: rs1554415096; hg19: chr7-141418986; COSMIC: COSV101285242; COSMIC: COSV101285242;