rs17730436

Positions:

• chr15-53650731-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182758.4(WDR72):​c.1962+14841A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.212 in 151,902 control chromosomes in the GnomAD database, including 3,840 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3840 hom., cov: 31)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0330

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.44 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.1962+14841A>G		intron_variant		ENST00000360509.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.1962+14841A>G		intron_variant		1	NM_182758.4	P4

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32215 AN: 151784 Hom.: 3827 Cov.: 31

Gnomad AFR AF: 0.150

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0900

Gnomad EAS AF: 0.455

Gnomad SAS AF: 0.241

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.115

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.200

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.212 AC: 32240 AN: 151902 Hom.: 3840 Cov.: 31 AF XY: 0.219 AC XY: 16233 AN XY: 74270

Gnomad4 AFR AF: 0.149

Gnomad4 AMR AF: 0.292

Gnomad4 ASJ AF: 0.0900

Gnomad4 EAS AF: 0.456

Gnomad4 SAS AF: 0.241

Gnomad4 FIN AF: 0.271

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.202

Alfa AF: 0.213 Hom.: 3193

Bravo AF: 0.213

Asia WGS AF: 0.349 AC: 1214 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.1
DANN	Benign	0.66

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: rs17730436; hg19: chr15-53942928;