15-53679974-C-T

Variant names:

• chr15-53679974-C-T
• rs989790
• NM_182758.4:c.1766-14206G>A

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 1 publications found

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 Gene-Disease associations (from GenCC):

• amelogenesis imperfecta

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• amelogenesis imperfecta hypomaturation type 2A3

  Inheritance: AR Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• amelogenesis imperfecta type 2

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• renal tubular acidosis

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_182758.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	NM_182758.4	MANE Select	c.1766-14206G>A		intron	N/A	NP_877435.3	Q3MJ13
	WDR72	NR_102334.2		n.2006-14206G>A		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	ENST00000360509.10	TSL:1 MANE Select	c.1766-14206G>A		intron	N/A	ENSP00000353699.5	Q3MJ13
	WDR72	ENST00000396328.5	TSL:1	c.1766-14206G>A		intron	N/A	ENSP00000379619.1	Q3MJ13
	WDR72	ENST00000559418.5	TSL:5	c.1796-14206G>A		intron	N/A	ENSP00000452765.1	H0YKE0

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

African (AFR) AF: 0.222 AC: 9101 AN: 40986

American (AMR) AF: 0.0310 AC: 469 AN: 15138

Ashkenazi Jewish (ASJ) AF: 0.000577 AC: 2 AN: 3466

East Asian (EAS) AF: 0.0689 AC: 354 AN: 5138

South Asian (SAS) AF: 0.0471 AC: 225 AN: 4778

European-Finnish (FIN) AF: 0.0192 AC: 193 AN: 10034

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.0127 AC: 860 AN: 67816

Other (OTH) AF: 0.0520 AC: 109 AN: 2096

Alfa AF: 0.0307 Hom.: 998

Bravo AF: 0.0827

Asia WGS AF: 0.0660 AC: 230 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.088
DANN	Benign	0.13
PhyloP100		-4.8
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs989790; hg19: chr15-53972171;