15-53679974-C-T

Position:

• chr15-53679974-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.1766-14206G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0751 in 150,652 control chromosomes in the GnomAD database, including 1,090 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 0.075 (1090 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -4.85

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]

WDR72 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.218 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4	c.1766-14206G>A		intron_variant		ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.1766-14206G>A		intron_variant		1	NM_182758.4	ENSP00000353699.5

Frequencies

GnomAD3 genomes AF: 0.0749 AC: 11281 AN: 150572 Hom.: 1082 Cov.: 32

Gnomad AFR AF: 0.222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0310

Gnomad ASJ AF: 0.000577

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.0474

Gnomad FIN AF: 0.0192

Gnomad MID AF: 0.0128

Gnomad NFE AF: 0.0127

Gnomad OTH AF: 0.0500

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

GnomAD4 genome AF: 0.0751 AC: 11314 AN: 150652 Hom.: 1090 Cov.: 32 AF XY: 0.0746 AC XY: 5484 AN XY: 73482

Gnomad4 AFR AF: 0.222

Gnomad4 AMR AF: 0.0310

Gnomad4 ASJ AF: 0.000577

Gnomad4 EAS AF: 0.0689

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0192

Gnomad4 NFE AF: 0.0127

Gnomad4 OTH AF: 0.0520

Alfa AF: 0.0177 Hom.: 152

Bravo AF: 0.0827

Asia WGS AF: 0.0660 AC: 230 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.088
DANN	Benign	0.13

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: rs989790; hg19: chr15-53972171;