chr4-183250473-G-C

Variant names:

• chr4-183250473-G-C
• rs4862152
• NM_024949.6:c.953+480G>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_024949.6(WWC2):​c.953+480G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.369 in 151,912 control chromosomes in the GnomAD database, including 10,415 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 0.37 (10415 hom., cov: 31)
• Consequence: WWC2 NM_024949.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.08
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.455 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC2	NM_024949.6	c.953+480G>C		intron_variant	Intron 8 of 22	ENST00000403733.8	NP_079225.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC2	ENST00000403733.8	c.953+480G>C		intron_variant	Intron 8 of 22	5	NM_024949.6	ENSP00000384222.3

Frequencies

GnomAD3 genomes AF: 0.369 AC: 55973 AN: 151794 Hom.: 10387 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.336

Gnomad ASJ AF: 0.345

Gnomad EAS AF: 0.306

Gnomad SAS AF: 0.470

Gnomad FIN AF: 0.393

Gnomad MID AF: 0.307

Gnomad NFE AF: 0.378

Gnomad OTH AF: 0.337

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

GnomAD4 genome AF: 0.369 AC: 56054 AN: 151912 Hom.: 10415 Cov.: 31 AF XY: 0.369 AC XY: 27395 AN XY: 74246

African (AFR) AF: 0.363 AC: 15042 AN: 41420

American (AMR) AF: 0.335 AC: 5125 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.345 AC: 1197 AN: 3468

East Asian (EAS) AF: 0.306 AC: 1576 AN: 5142

South Asian (SAS) AF: 0.471 AC: 2259 AN: 4798

European-Finnish (FIN) AF: 0.393 AC: 4140 AN: 10524

Middle Eastern (MID) AF: 0.310 AC: 91 AN: 294

European-Non Finnish (NFE) AF: 0.378 AC: 25679 AN: 67962

Other (OTH) AF: 0.335 AC: 706 AN: 2108

Alfa AF: 0.222 Hom.: 491

Bravo AF: 0.361

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.10
DANN	Benign	0.52
PhyloP100		-2.1
Mutation Taster		=100/0	polymorphism (auto)

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: rs4862152; hg19: chr4-184171626;