chr4-183294522-A-G

Variant names:

• chr4-183294522-A-G
• rs955748
• NM_024949.6:c.3384+4887A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 40 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=-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 rank	MANE	Protein	UniProt
WWC2	NM_024949.6	c.3384+4887A>G		intron_variant	Intron 21 of 22	ENST00000403733.8	NP_079225.5
WWC2	NM_001410864.1	c.3456+4887A>G		intron_variant	Intron 21 of 22		NP_001397793.1
WWC2	XM_024454225.2	c.3162+4887A>G		intron_variant	Intron 20 of 21		XP_024309993.1
WWC2	XM_047416198.1	c.3090+4887A>G		intron_variant	Intron 20 of 21		XP_047272154.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC2	ENST00000403733.8	c.3384+4887A>G		intron_variant	Intron 21 of 22	5	NM_024949.6	ENSP00000384222.3

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

African (AFR) AF: 0.548 AC: 22740 AN: 41466

American (AMR) AF: 0.701 AC: 10722 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.770 AC: 2673 AN: 3470

East Asian (EAS) AF: 0.555 AC: 2864 AN: 5162

South Asian (SAS) AF: 0.688 AC: 3319 AN: 4826

European-Finnish (FIN) AF: 0.778 AC: 8228 AN: 10570

Middle Eastern (MID) AF: 0.759 AC: 223 AN: 294

European-Non Finnish (NFE) AF: 0.761 AC: 51749 AN: 67998

Other (OTH) AF: 0.691 AC: 1458 AN: 2110

Alfa AF: 0.735 Hom.: 181506

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
PhyloP100		-2.5
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: rs955748; hg19: chr4-184215675;