rs1554415096

Variant names:

• chr7-141719186-G-A
• rs1554415096
• NM_001105558.1:c.700G>A

Your query was ambiguous. Multiple possible variants found:

• chr7-141719186-G-A
• chr7-141719186-G-C
• chr7-141719186-G-T

Variant summary

Our verdict is Uncertain significance. The variant received 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
• 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 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 VariationId is 545469.Status of the report is no_assertion_criteria_provided, 0 stars.

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WEE2	NM_001105558.1	MANE Select	c.700G>A	p.Asp234Asn	missense	Exon 4 of 12	NP_001099028.1
	WEE2-AS1	NR_015392.1		n.656+4730C>T		intron	N/A
	WEE2-AS1	NR_199840.1		n.923+4730C>T		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WEE2	ENST00000397541.6	TSL:1 MANE Select	c.700G>A	p.Asp234Asn	missense	Exon 4 of 12	ENSP00000380675.2
	WEE2-AS1	ENST00000462383.6	TSL:1	n.412+4730C>T		intron	N/A
	WEE2-AS1	ENST00000465110.5	TSL:1	n.132+4730C>T		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
MetaSVM	Uncertain	0.0090	D
MutationAssessor	Benign	2.0	M
PhyloP100		9.5
PrimateAI	Uncertain	0.53	T
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.48
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	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
PromoterAI		-0.00060	Neutral
Varity_R		0.86
gMVP		0.64
Mutation Taster		=24/76	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: rs1554415096; hg19: chr7-141418986; COSMIC: COSV101285242; COSMIC: COSV101285242;