rs17074417

Positions:

• chr4-183125003-A-G
• chr4-183125003-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.131+25381A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0582 in 152,248 control chromosomes in the GnomAD database, including 406 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 0.058 (406 hom., cov: 32)
• Consequence: WWC2 NM_024949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.234

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 (AFR) allele frequency at 95% confidence interval = 0.122 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WWC2	NM_024949.6	c.131+25381A>G		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+25381A>G		intron_variant		5	NM_024949.6	ENSP00000384222.3
WWC2	ENST00000448232.6	c.131+25381A>G		intron_variant		5		ENSP00000398577.2
WWC2	ENST00000513834.5	c.131+25381A>G		intron_variant		5		ENSP00000425054.1
WWC2	ENST00000508614.5	n.131+25381A>G		intron_variant		3		ENSP00000423238.1

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8849 AN: 152130 Hom.: 408 Cov.: 32

Gnomad AFR AF: 0.125

Gnomad AMI AF: 0.0998

Gnomad AMR AF: 0.0280

Gnomad ASJ AF: 0.0594

Gnomad EAS AF: 0.0100

Gnomad SAS AF: 0.0329

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.0285

Gnomad NFE AF: 0.0372

Gnomad OTH AF: 0.0450

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

GnomAD4 genome AF: 0.0582 AC: 8864 AN: 152248 Hom.: 406 Cov.: 32 AF XY: 0.0549 AC XY: 4090 AN XY: 74438

Gnomad4 AFR AF: 0.125

Gnomad4 AMR AF: 0.0280

Gnomad4 ASJ AF: 0.0594

Gnomad4 EAS AF: 0.0100

Gnomad4 SAS AF: 0.0327

Gnomad4 FIN AF: 0.0112

Gnomad4 NFE AF: 0.0372

Gnomad4 OTH AF: 0.0460

Alfa AF: 0.0380 Hom.: 64

Bravo AF: 0.0614

Asia WGS AF: 0.0440 AC: 153 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	2.2
DANN	Benign	0.29

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: rs17074417; hg19: chr4-184046156;