rs955748

chr4-183294522-A-Gchr4-183294522-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024949.6(WWC2):c.3384+4887A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.688 in 152,104 control chromosomes in the GnomAD database, including 36,655 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.69 (36655 hom., cov: 32)
• Consequence: WWC2 NM_024949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.50

Genes affected

WWC2 (HGNC:24148): (WW and C2 domain containing 2) This gene encodes a member of the WW-and-C2-domain-containing family of proteins. Members of this family have two N-terminal WW domains that mediate binding to target proteins harboring L/PPxY motifs, an internal C2 domain for membrane association, and C-terminal alpha protein kinase C binding sites and class III PDZ domain-interaction motifs. Proteins of this family are able to form homo- and heterodimers and to modulate hippo pathway signaling. [provided by RefSeq, Sep 2016]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.04).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.756 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC2	NM_024949.6	c.3384+4887A>G		intron_variant		ENST00000403733.8
WWC2	NM_001410864.1	c.3456+4887A>G		intron_variant
WWC2	XM_024454225.2	c.3162+4887A>G		intron_variant
WWC2	XM_047416198.1	c.3090+4887A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC2	ENST00000403733.8	c.3384+4887A>G		intron_variant		5	NM_024949.6	P1

Frequencies

GnomAD3 genomes AF: 0.688 AC: 104503 AN: 151986 Hom.: 36613 Cov.: 32

Gnomad AFR AF: 0.548

Gnomad AMI AF: 0.689

Gnomad AMR AF: 0.701

Gnomad ASJ AF: 0.770

Gnomad EAS AF: 0.554

Gnomad SAS AF: 0.686

Gnomad FIN AF: 0.778

Gnomad MID AF: 0.759

Gnomad NFE AF: 0.761

Gnomad OTH AF: 0.692

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.688 AC: 104602 AN: 152104 Hom.: 36655 Cov.: 32 AF XY: 0.689 AC XY: 51231 AN XY: 74374

Gnomad4 AFR AF: 0.548

Gnomad4 AMR AF: 0.701

Gnomad4 ASJ AF: 0.770

Gnomad4 EAS AF: 0.555

Gnomad4 SAS AF: 0.688

Gnomad4 FIN AF: 0.778

Gnomad4 NFE AF: 0.761

Gnomad4 OTH AF: 0.691

Alfa AF: 0.747 Hom.: 84194

Bravo AF: 0.675

Asia WGS AF: 0.615 AC: 2141 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
Cadd	Benign	0.66
Dann	Benign	0.33

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: rs955748; hg19: chr4-184215675;