chr10-28533659-G-GGGCGGC

Position:

• chr10-28533659-G-GGGCGGC

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_016628.5(WAC):​c.41+45_41+50dupCGGCGG variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00192 in 1,540,618 control chromosomes in the GnomAD database, including 55 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.010 (28 hom., cov: 32)
  • Exomes 𝑓: 0.0010 (27 hom.)
• Consequence: WAC NM_016628.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.40

Genes affected

WAC (HGNC:17327): (WW domain containing adaptor with coiled-coil) The protein encoded by this gene contains a WW domain, which is a protein module found in a wide range of signaling proteins. This domain mediates protein-protein interactions and binds proteins containing short linear peptide motifs that are proline-rich or contain at least one proline. This gene product shares 94% sequence identity with the WAC protein in mouse, however, its exact function is not known. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Dec 2008]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 10-28533659-G-GGGCGGC is Benign according to our data. Variant chr10-28533659-G-GGGCGGC is described in ClinVar as [Likely_benign]. Clinvar id is 1219860.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0103 (1560/150948) while in subpopulation AFR AF= 0.0358 (1475/41216). AF 95% confidence interval is 0.0343. There are 28 homozygotes in gnomad4. There are 773 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1560 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WAC	NM_016628.5	c.41+45_41+50dupCGGCGG		intron_variant		ENST00000354911.9	NP_057712.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WAC	ENST00000354911.9	c.41+39_41+40insGGCGGC		intron_variant		1	NM_016628.5	ENSP00000346986.4
WAC	ENST00000428935.6	c.-94-339_-94-338insGGCGGC		intron_variant		2		ENSP00000399706.3
WAC	ENST00000651885.1	c.41+39_41+40insGGCGGC		intron_variant				ENSP00000498678.1
WAC	ENST00000651598.1	c.-112-339_-112-338insGGCGGC		intron_variant				ENSP00000498480.1

Frequencies

GnomAD3 genomes AF: 0.0103 AC: 1559 AN: 150838 Hom.: 28 Cov.: 32

Gnomad AFR AF: 0.0359

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00447

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00338

Gnomad NFE AF: 0.0000740

Gnomad OTH AF: 0.00530

GnomAD3 exomes AF: 0.00240 AC: 367 AN: 152914 Hom.: 19 AF XY: 0.00219 AC XY: 183 AN XY: 83516

Gnomad AFR exome AF: 0.0469

Gnomad AMR exome AF: 0.00236

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000133

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000148

Gnomad OTH exome AF: 0.00118

GnomAD4 exome AF: 0.00100 AC: 1391 AN: 1389670 Hom.: 27 Cov.: 29 AF XY: 0.000888 AC XY: 610 AN XY: 686906

Gnomad4 AFR exome AF: 0.0362

Gnomad4 AMR exome AF: 0.00255

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000127

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000260

Gnomad4 OTH exome AF: 0.00266

GnomAD4 genome AF: 0.0103 AC: 1560 AN: 150948 Hom.: 28 Cov.: 32 AF XY: 0.0105 AC XY: 773 AN XY: 73746

Gnomad4 AFR AF: 0.0358

Gnomad4 AMR AF: 0.00446

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000740

Gnomad4 OTH AF: 0.00524

Alfa AF: 0.000342 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 19, 2020

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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: rs749860033; hg19: chr10-28822588;