rs491567

Variant names:

• chr15-53654396-A-C
• rs491567
• NM_182758.4:c.1962+11176T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-53654396-A-C
• chr15-53654396-A-G
• chr15-53654396-A-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_182758.4(WDR72):​c.1962+11176T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.342 in 152,122 control chromosomes in the GnomAD database, including 10,718 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 0.34 (10718 hom., cov: 33)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.143
• Publications: 35 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.552 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.1962+11176T>G		intron	N/A	NP_877435.3	Q3MJ13
	WDR72	NR_102334.2		n.2202+11176T>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	ENST00000360509.10	TSL:1 MANE Select	c.1962+11176T>G		intron	N/A	ENSP00000353699.5	Q3MJ13
	WDR72	ENST00000396328.5	TSL:1	c.1962+11176T>G		intron	N/A	ENSP00000379619.1	Q3MJ13
	WDR72	ENST00000559418.5	TSL:5	c.1992+11176T>G		intron	N/A	ENSP00000452765.1	H0YKE0

Frequencies

GnomAD3 genomes AF: 0.341 AC: 51878 AN: 152006 Hom.: 10664 Cov.: 33

Gnomad AFR AF: 0.557

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.341

Gnomad ASJ AF: 0.0906

Gnomad EAS AF: 0.527

Gnomad SAS AF: 0.287

Gnomad FIN AF: 0.292

Gnomad MID AF: 0.137

Gnomad NFE AF: 0.225

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.342 AC: 51997 AN: 152122 Hom.: 10718 Cov.: 33 AF XY: 0.346 AC XY: 25756 AN XY: 74364

African (AFR) AF: 0.558 AC: 23133 AN: 41470

American (AMR) AF: 0.342 AC: 5228 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0906 AC: 314 AN: 3466

East Asian (EAS) AF: 0.527 AC: 2731 AN: 5178

South Asian (SAS) AF: 0.287 AC: 1381 AN: 4814

European-Finnish (FIN) AF: 0.292 AC: 3093 AN: 10590

Middle Eastern (MID) AF: 0.120 AC: 35 AN: 292

European-Non Finnish (NFE) AF: 0.225 AC: 15309 AN: 67998

Other (OTH) AF: 0.300 AC: 633 AN: 2112

Alfa AF: 0.274 Hom.: 13601

Bravo AF: 0.357

Asia WGS AF: 0.433 AC: 1504 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.4
DANN	Benign	0.82
PhyloP100		-0.14
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: rs491567; hg19: chr15-53946593;