rs10518733

Variant names:

• chr15-53648110-A-C
• rs10518733
• NM_182758.4:c.1962+17462T>G

Your query was ambiguous. Multiple possible variants found:

• chr15-53648110-A-C
• chr15-53648110-A-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.1962+17462T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 152,020 control chromosomes in the GnomAD database, including 3,887 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 0.21 (3887 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0570
• Publications: 16 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=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.443 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.1962+17462T>G		intron_variant	Intron 14 of 19	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.1962+17462T>G		intron_variant	Intron 14 of 19	1	NM_182758.4	ENSP00000353699.5

Frequencies

GnomAD3 genomes AF: 0.214 AC: 32498 AN: 151902 Hom.: 3873 Cov.: 32

Gnomad AFR AF: 0.156

Gnomad AMI AF: 0.154

Gnomad AMR AF: 0.292

Gnomad ASJ AF: 0.0897

Gnomad EAS AF: 0.459

Gnomad SAS AF: 0.239

Gnomad FIN AF: 0.271

Gnomad MID AF: 0.117

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.200

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

GnomAD4 genome AF: 0.214 AC: 32527 AN: 152020 Hom.: 3887 Cov.: 32 AF XY: 0.220 AC XY: 16368 AN XY: 74352

African (AFR) AF: 0.156 AC: 6456 AN: 41510

American (AMR) AF: 0.292 AC: 4460 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.0897 AC: 311 AN: 3466

East Asian (EAS) AF: 0.459 AC: 2358 AN: 5138

South Asian (SAS) AF: 0.239 AC: 1153 AN: 4830

European-Finnish (FIN) AF: 0.271 AC: 2871 AN: 10596

Middle Eastern (MID) AF: 0.109 AC: 32 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14319 AN: 67918

Other (OTH) AF: 0.203 AC: 427 AN: 2102

Alfa AF: 0.208 Hom.: 16343

Bravo AF: 0.215

Asia WGS AF: 0.347 AC: 1206 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	1.4
DANN	Benign	0.59
PhyloP100		-0.057
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: rs10518733; hg19: chr15-53940307;