rs16966247

Variant names:

• chr15-53589748-G-C
• rs16966247
• NM_182758.4:c.3148+7331C>G

Variant summary

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

The NM_182758.4(WDR72):​c.3148+7331C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0986 in 152,004 control chromosomes in the GnomAD database, including 898 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 0.099 (898 hom., cov: 33)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.53
• 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=-0.63).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.157 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.3148+7331C>G		intron_variant	Intron 18 of 19	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.3148+7331C>G		intron_variant	Intron 18 of 19	1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328.5	c.3148+7331C>G		intron_variant	Intron 18 of 19	1		ENSP00000379619.1
WDR72	ENST00000559418.5	c.3178+7331C>G		intron_variant	Intron 17 of 18	5		ENSP00000452765.1
WDR72	ENST00000557913.5	c.3139+7331C>G		intron_variant	Intron 18 of 19	5		ENSP00000453378.1

Frequencies

GnomAD3 genomes AF: 0.0985 AC: 14959 AN: 151886 Hom.: 896 Cov.: 33

Gnomad AFR AF: 0.160

Gnomad AMI AF: 0.128

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.0620

Gnomad EAS AF: 0.0136

Gnomad SAS AF: 0.125

Gnomad FIN AF: 0.0960

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0662

Gnomad OTH AF: 0.0861

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

GnomAD4 genome AF: 0.0986 AC: 14987 AN: 152004 Hom.: 898 Cov.: 33 AF XY: 0.101 AC XY: 7497 AN XY: 74298

African (AFR) AF: 0.160 AC: 6637 AN: 41464

American (AMR) AF: 0.107 AC: 1629 AN: 15246

Ashkenazi Jewish (ASJ) AF: 0.0620 AC: 215 AN: 3468

East Asian (EAS) AF: 0.0136 AC: 70 AN: 5150

South Asian (SAS) AF: 0.125 AC: 603 AN: 4826

European-Finnish (FIN) AF: 0.0960 AC: 1017 AN: 10598

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0662 AC: 4499 AN: 67934

Other (OTH) AF: 0.0857 AC: 181 AN: 2112

Alfa AF: 0.0876 Hom.: 88

Bravo AF: 0.101

Asia WGS AF: 0.0690 AC: 239 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	14
DANN	Benign	0.61
PhyloP100		1.5
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: rs16966247; hg19: chr15-53881945;