rs11132168

Positions:

• chr4-183132034-C-T

Variant summary

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

The NM_024949.6(WWC2):​c.131+32412C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.109 in 152,026 control chromosomes in the GnomAD database, including 1,352 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 0.11 (1352 hom., cov: 32)
• Consequence: WWC2 NM_024949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.493

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=-0.88).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.246 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC2	NM_024949.6	c.131+32412C>T		intron_variant		ENST00000403733.8	NP_079225.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WWC2	ENST00000403733.8	c.131+32412C>T		intron_variant		5	NM_024949.6	ENSP00000384222	P1
WWC2	ENST00000448232.6	c.131+32412C>T		intron_variant		5		ENSP00000398577
WWC2	ENST00000513834.5	c.131+32412C>T		intron_variant		5		ENSP00000425054
WWC2	ENST00000508614.5	c.131+32412C>T		intron_variant, NMD_transcript_variant		3		ENSP00000423238

Frequencies

GnomAD3 genomes AF: 0.109 AC: 16600 AN: 151908 Hom.: 1344 Cov.: 32

Gnomad AFR AF: 0.0247

Gnomad AMI AF: 0.121

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.0533

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.0997

Gnomad FIN AF: 0.186

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.114

Gnomad OTH AF: 0.116

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

GnomAD4 genome AF: 0.109 AC: 16613 AN: 152026 Hom.: 1352 Cov.: 32 AF XY: 0.116 AC XY: 8587 AN XY: 74302

Gnomad4 AFR AF: 0.0246

Gnomad4 AMR AF: 0.252

Gnomad4 ASJ AF: 0.0533

Gnomad4 EAS AF: 0.195

Gnomad4 SAS AF: 0.0990

Gnomad4 FIN AF: 0.186

Gnomad4 NFE AF: 0.114

Gnomad4 OTH AF: 0.117

Alfa AF: 0.109 Hom.: 649

Bravo AF: 0.111

Asia WGS AF: 0.142 AC: 493 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	7.7
DANN	Benign	0.70

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: rs11132168; hg19: chr4-184053187;