5-168431457-TCTGGCTGGCTGGCTGGCTGGCTGGCTGG-TCTGG

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_015238.3(WWC1):c.2280+37_2280+60del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000158 in 1,414,550 control chromosomes in the GnomAD database, including 1 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00016 (1 hom.)
• Consequence: WWC1 NM_015238.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.31

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WWC1	NM_015238.3	c.2280+37_2280+60del		intron_variant		ENST00000265293.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WWC1	ENST00000265293.9	c.2280+37_2280+60del		intron_variant		1	NM_015238.3	P1

Frequencies

GnomAD3 genomes AF: 0.000182 AC: 27 AN: 148350 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.0000747

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000135

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00113

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000253

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.000237 AC: 30 AN: 126504 Hom.: 0 AF XY: 0.000221 AC XY: 15 AN XY: 68006

Gnomad AFR exome AF: 0.000109

Gnomad AMR exome AF: 0.000397

Gnomad ASJ exome AF: 0.000267

Gnomad EAS exome AF: 0.000181

Gnomad SAS exome AF: 0.000287

Gnomad FIN exome AF: 0.000174

Gnomad NFE exome AF: 0.000219

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.000156 AC: 197 AN: 1266090 Hom.: 1 AF XY: 0.000180 AC XY: 113 AN XY: 628354

Gnomad4 AFR exome AF: 0.000139

Gnomad4 AMR exome AF: 0.000402

Gnomad4 ASJ exome AF: 0.0000974

Gnomad4 EAS exome AF: 0.0000277

Gnomad4 SAS exome AF: 0.000705

Gnomad4 FIN exome AF: 0.0000281

Gnomad4 NFE exome AF: 0.000121

Gnomad4 OTH exome AF: 0.000113

GnomAD4 genome AF: 0.000182 AC: 27 AN: 148460 Hom.: 0 Cov.: 0 AF XY: 0.000152 AC XY: 11 AN XY: 72194

Gnomad4 AFR AF: 0.0000745

Gnomad4 AMR AF: 0.000134

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00113

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000253

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11279828; hg19: chr5-167858462;