Genetic Variant WWC1:c.2280+57_2280+60delGCTG (chr5-168431457-TCTGG-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_015238.3(WWC1):c.2280+57_2280+60delGCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.387 in 1,406,984 control chromosomes in the GnomAD database, including 105,519 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.38 ( 11745 hom., cov: 0)

Exomes 𝑓: 0.39 ( 93774 hom. )

Consequence

WWC1
NM_015238.3 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.527

Variant links:

Genes affected

WWC1 (HGNC:29435): (WW and C2 domain containing 1) The protein encoded by this gene is a cytoplasmic phosphoprotein that interacts with PRKC-zeta and dynein light chain-1. Alleles of this gene have been found that enhance memory in some individuals. Three transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Mar 2010]

WWC1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 5-168431457-TCTGG-T is Benign according to our data. Variant chr5-168431457-TCTGG-T is described in ClinVar as [Benign]. Clinvar id is 403611.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3 link	c.2280+57_2280+60delGCTG		intron_variant	Intron 15 of 22	ENST00000265293.9	NP_056053.1	Q8IX03-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WWC1	ENST00000265293.9 link	c.2280+14_2280+17delCTGG		intron_variant	Intron 15 of 22	1	NM_015238.3	ENSP00000265293.4		Q8IX03-1

Frequencies

GnomAD3 genomes

AF:

0.384

AC:

56792

AN:

148060

Hom.:

11741

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.344

Gnomad AMR

AF:

0.391

Gnomad ASJ

AF:

0.424

Gnomad EAS

AF:

0.193

Gnomad SAS

AF:

0.402

Gnomad FIN

AF:

0.467

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.463

Gnomad OTH

AF:

0.428

GnomAD3 exomes

AF:

0.349

AC:

44091

AN:

126504

Hom.:

8000

AF XY:

0.357

AC XY:

24246

AN XY:

68006

show subpopulations

Gnomad AFR exome

AF:

0.210

Gnomad AMR exome

AF:

0.313

Gnomad ASJ exome

AF:

0.365

Gnomad EAS exome

AF:

0.186

Gnomad SAS exome

AF:

0.370

Gnomad FIN exome

AF:

0.376

Gnomad NFE exome

AF:

0.401

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.388

AC:

488354

AN:

1258818

Hom.:

93774

AF XY:

0.390

AC XY:

243934

AN XY:

624868

show subpopulations

Gnomad4 AFR exome

AF:

0.223

Gnomad4 AMR exome

AF:

0.310

Gnomad4 ASJ exome

AF:

0.394

Gnomad4 EAS exome

AF:

0.221

Gnomad4 SAS exome

AF:

0.379

Gnomad4 FIN exome

AF:

0.411

Gnomad4 NFE exome

AF:

0.401

Gnomad4 OTH exome

AF:

0.389

GnomAD4 genome

AF:

0.383

AC:

56818

AN:

148166

Hom.:

11745

Cov.:

AF XY:

0.381

AC XY:

27476

AN XY:

72038

show subpopulations

Gnomad4 AFR

AF:

0.244

Gnomad4 AMR

AF:

0.391

Gnomad4 ASJ

AF:

0.424

Gnomad4 EAS

AF:

0.192

Gnomad4 SAS

AF:

0.403

Gnomad4 FIN

AF:

0.467

Gnomad4 NFE

AF:

0.463

Gnomad4 OTH

AF:

0.429

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Mar 28, 2016

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Frequency -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

Below is the list of publications found by LitVar. It may be empty.

5-168431457-TCTGGCTGGCTGGCTGGCTGGCTGGCTGGCTGG-TCTGGCTGGCTGGCTGGCTGGCTGGCTGG

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over