rs690054

Positions:

• chr15-53708776-C-T

Variant summary

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

The NM_182758.4(WDR72):​c.954+2081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,986 control chromosomes in the GnomAD database, including 12,351 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 0.38 (12351 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195

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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR72	NM_182758.4	c.954+2081G>A		intron_variant		ENST00000360509.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR72	ENST00000360509.10	c.954+2081G>A		intron_variant		1	NM_182758.4	P4

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57737 AN: 151866 Hom.: 12357 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.380 AC: 57724 AN: 151986 Hom.: 12351 Cov.: 32 AF XY: 0.373 AC XY: 27680 AN XY: 74290

Gnomad4 AFR AF: 0.208

Gnomad4 AMR AF: 0.370

Gnomad4 ASJ AF: 0.627

Gnomad4 EAS AF: 0.202

Gnomad4 SAS AF: 0.461

Gnomad4 FIN AF: 0.317

Gnomad4 NFE AF: 0.487

Gnomad4 OTH AF: 0.420

Alfa AF: 0.474 Hom.: 17320

Bravo AF: 0.372

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
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: rs690054; hg19: chr15-54000973;