rs606231351

chr15-53613680-CT-C

Variant summary

Our verdict is Pathogenic. Variant got 11 ACMG points: 11P and 0B. PVS1 PM2 PP5

The NM_182758.4(WDR72):c.2857del(p.Ser953ValfsTer20) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Pathogenic (no stars). Variant results in nonsense mediated mRNA decay.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR72 NM_182758.4 frameshift
• Clinical Significance: Pathogenic no assertion criteria provided P:2
• Conservation: PhyloP100: -0.948

Genes affected

WDR72 (HGNC:26790): (WD repeat domain 72) This gene encodes a protein with eight WD-40 repeats. Mutations in this gene have been associated with amelogenesis imperfecta hypomaturation type 2A3. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2013]

ACMG classification

Verdict is Pathogenic. Variant got 11 ACMG points.

• PVS1: Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.
• PM2: Very rare variant in population databases, with high coverage
• PP5: Variant 15-53613680-CT-C is Pathogenic according to our data. Variant chr15-53613680-CT-C is described in ClinVar as [Pathogenic]. Clinvar id is 233.Status of the report is no_assertion_criteria_provided, 0 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.2857del	p.Ser953ValfsTer20	frameshift_variant	16/20	ENST00000360509.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.2857del	p.Ser953ValfsTer20	frameshift_variant	16/20	1	NM_182758.4	P4
WDR72	ENST00000396328.5	c.2857del	p.Ser953ValfsTer20	frameshift_variant	16/20	1		P4
WDR72	ENST00000559418.5	c.2887del	p.Ser963ValfsTer20	frameshift_variant	15/19	5
WDR72	ENST00000557913.5	c.2848del	p.Ser950ValfsTer20	frameshift_variant	16/20	5		A1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

GnomAD4 genome Cov.: 32

ClinVar

Significance: Pathogenic

Submissions summary: Pathogenic:2

Revision: no assertion criteria provided

Submissions by phenotype

Amelogenesis imperfecta hypomaturation type 2A3 Pathogenic:2

Pathogenic, no assertion criteria provided	literature only	OMIM	Nov 01, 2009	- -
Pathogenic, no assertion criteria provided	curation	Department Of Genetics, Sultan Qaboos University Hospital, Sultan Qaboos University	Dec 30, 2017	- -

Computational scores

Source: dbNSFP v4.3

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: rs606231351; hg19: chr15-53905877;