rs572930

chr15-53660998-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+4574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,160 control chromosomes in the GnomAD database, including 1,598 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 0.089 (1598 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843

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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.1962+4574A>G		intron_variant		ENST00000360509.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.1962+4574A>G		intron_variant		1	NM_182758.4	P4

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13558 AN: 152042 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0894 AC: 13602 AN: 152160 Hom.: 1598 Cov.: 32 AF XY: 0.0888 AC XY: 6607 AN XY: 74410

Gnomad4 AFR AF: 0.270

Gnomad4 AMR AF: 0.0359

Gnomad4 ASJ AF: 0.000864

Gnomad4 EAS AF: 0.0688

Gnomad4 SAS AF: 0.0498

Gnomad4 FIN AF: 0.0202

Gnomad4 NFE AF: 0.0135

Gnomad4 OTH AF: 0.0663

Alfa AF: 0.0552 Hom.: 123

Bravo AF: 0.0974

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.64
Dann	Benign	0.51

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: rs572930; hg19: chr15-53953195;