Genetic Variant NM_015238.3:c.2280+49_2280+60delGCTGGCTGGCTG (chr5-168431457-TCTGGCTGGCTGG-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_015238.3(WWC1):c.2280+49_2280+60delGCTGGCTGGCTG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0097 in 1,391,202 control chromosomes in the GnomAD database, including 400 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 224 hom., cov: 0)

Exomes 𝑓: 0.0072 ( 176 hom. )

Consequence

WWC1
NM_015238.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.31

Publications

2 publications found

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.099 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WWC1	NM_015238.3 link	c.2280+49_2280+60delGCTGGCTGGCTG		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+25delCTGGCTGGCTGG		intron_variant	Intron 15 of 22	1	NM_015238.3	ENSP00000265293.4		Q8IX03-1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4531

AN:

148286

Hom.:

221

Cov.:

show subpopulations

Gnomad AFR

AF:

0.101

Gnomad AMI

AF:

0.00111

Gnomad AMR

AF:

0.0112

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00100

Gnomad SAS

AF:

0.00723

Gnomad FIN

AF:

0.0000985

Gnomad MID

AF:

0.00962

Gnomad NFE

AF:

0.00307

Gnomad OTH

AF:

0.0235

GnomAD2 exomes

AF:

0.0154

AC:

1945

AN:

126504

AF XY:

0.0140

show subpopulations

Gnomad AFR exome

AF:

0.112

Gnomad AMR exome

AF:

0.0128

Gnomad ASJ exome

AF:

0.00241

Gnomad EAS exome

AF:

0.00642

Gnomad FIN exome

AF:

0.00313

Gnomad NFE exome

AF:

0.00584

Gnomad OTH exome

AF:

0.0103

GnomAD4 exome

AF:

0.00720

AC:

8944

AN:

1242810

Hom.:

176

AF XY:

0.00701

AC XY:

4320

AN XY:

616508

show subpopulations

African (AFR)

AF:

0.114

AC:

3212

AN:

28076

American (AMR)

AF:

0.0111

AC:

345

AN:

31176

Ashkenazi Jewish (ASJ)

AF:

0.00109

AC:

AN:

20092

East Asian (EAS)

AF:

0.00258

AC:

AN:

34546

South Asian (SAS)

AF:

0.0105

AC:

714

AN:

67746

European-Finnish (FIN)

AF:

0.000801

AC:

AN:

34938

Middle Eastern (MID)

AF:

0.0101

AC:

AN:

4638

European-Non Finnish (NFE)

AF:

0.00397

AC:

3846

AN:

969384

Other (OTH)

AF:

0.0123

AC:

641

AN:

52214

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.508

Heterozygous variant carriers

350

700

1051

1401

1751

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

212

424

636

848

1060

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0307

AC:

4551

AN:

148392

Hom.:

224

Cov.:

AF XY:

0.0290

AC XY:

2093

AN XY:

72160

show subpopulations

African (AFR)

AF:

0.102

AC:

4088

AN:

40246

American (AMR)

AF:

0.0113

AC:

168

AN:

14866

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3430

East Asian (EAS)

AF:

0.00101

AC:

AN:

4966

South Asian (SAS)

AF:

0.00724

AC:

AN:

4420

European-Finnish (FIN)

AF:

0.0000985

AC:

AN:

10154

Middle Eastern (MID)

AF:

0.0103

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.00307

AC:

206

AN:

67096

Other (OTH)

AF:

0.0232

AC:

AN:

2022

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

202

404

605

807

1009

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00872

Hom.:

1588

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

2.3

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over