4-183261091-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_024949.6(WWC2):c.1468C>T(p.Leu490=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00536 in 1,613,994 control chromosomes in the GnomAD database, including 363 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.029 (204 hom., cov: 32)
  • Exomes 𝑓: 0.0029 (159 hom.)
• Consequence: WWC2 NM_024949.6 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.35

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 -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.28).
• BP6: Variant 4-183261091-C-T is Benign according to our data. Variant chr4-183261091-C-T is described in ClinVar as [Benign]. Clinvar id is 780936.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.35 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0983 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC2	NM_024949.6	c.1468C>T	p.Leu490=	synonymous_variant	11/23	ENST00000403733.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC2	ENST00000403733.8	c.1468C>T	p.Leu490=	synonymous_variant	11/23	5	NM_024949.6	P1

Frequencies

GnomAD3 genomes AF: 0.0288 AC: 4386 AN: 152184 Hom.: 202 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00896

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.000500

Gnomad OTH AF: 0.0191

GnomAD3 exomes AF: 0.00733 AC: 1840 AN: 251006 Hom.: 76 AF XY: 0.00557 AC XY: 756 AN XY: 135676

Gnomad AFR exome AF: 0.0991

Gnomad AMR exome AF: 0.00526

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.0000980

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000203

Gnomad OTH exome AF: 0.00359

GnomAD4 exome AF: 0.00290 AC: 4241 AN: 1461692 Hom.: 159 Cov.: 32 AF XY: 0.00246 AC XY: 1789 AN XY: 727122

Gnomad4 AFR exome AF: 0.0975

Gnomad4 AMR exome AF: 0.00568

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000255

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000251

Gnomad4 OTH exome AF: 0.00669

GnomAD4 genome AF: 0.0289 AC: 4409 AN: 152302 Hom.: 204 Cov.: 32 AF XY: 0.0284 AC XY: 2115 AN XY: 74474

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.00895

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000500

Gnomad4 OTH AF: 0.0189

Alfa AF: 0.0133 Hom.: 35

Bravo AF: 0.0330

Asia WGS AF: 0.00693 AC: 24 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000415

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Apr 19, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.28
Cadd	Benign	13
Dann	Benign	0.80

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: rs73872306; hg19: chr4-184182244;