rs572930

Variant names:

• chr15-53660998-T-C
• rs572930
• NM_182758.4:c.1962+4574A>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+4574A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0894 in 152,160 control chromosomes in the GnomAD database, including 1,598 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 0.089 (1598 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.843
• Publications: 0 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=-0.94).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.1962+4574A>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+4574A>G		intron_variant	Intron 14 of 19	1	NM_182758.4	ENSP00000353699.5

Frequencies

GnomAD3 genomes AF: 0.0892 AC: 13558 AN: 152042 Hom.: 1590 Cov.: 32

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0360

Gnomad ASJ AF: 0.000864

Gnomad EAS AF: 0.0691

Gnomad SAS AF: 0.0501

Gnomad FIN AF: 0.0202

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0135

Gnomad OTH AF: 0.0617

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

GnomAD4 genome AF: 0.0894 AC: 13602 AN: 152160 Hom.: 1598 Cov.: 32 AF XY: 0.0888 AC XY: 6607 AN XY: 74410

African (AFR) AF: 0.270 AC: 11178 AN: 41476

American (AMR) AF: 0.0359 AC: 549 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.000864 AC: 3 AN: 3472

East Asian (EAS) AF: 0.0688 AC: 356 AN: 5172

South Asian (SAS) AF: 0.0498 AC: 240 AN: 4824

European-Finnish (FIN) AF: 0.0202 AC: 214 AN: 10620

Middle Eastern (MID) AF: 0.0102 AC: 3 AN: 294

European-Non Finnish (NFE) AF: 0.0135 AC: 919 AN: 67996

Other (OTH) AF: 0.0663 AC: 140 AN: 2112

Alfa AF: 0.0552 Hom.: 123

Bravo AF: 0.0974

Asia WGS AF: 0.0740 AC: 259 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.64
DANN	Benign	0.51
PhyloP100		-0.84
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: rs572930; hg19: chr15-53953195;