chr15-53708776-C-T

Variant names:

• chr15-53708776-C-T
• rs690054
• NM_182758.4:c.954+2081G>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.954+2081G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.38 in 151,986 control chromosomes in the GnomAD database, including 12,351 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 0.38 (12351 hom., cov: 32)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.195
• Publications: 6 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=-0.88).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.482 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.954+2081G>A		intron	N/A	NP_877435.3	Q3MJ13
	WDR72	NR_102334.2		n.1194+2081G>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.954+2081G>A		intron	N/A	ENSP00000353699.5	Q3MJ13
	WDR72	ENST00000396328.5	TSL:1	c.954+2081G>A		intron	N/A	ENSP00000379619.1	Q3MJ13
	WDR72	ENST00000559418.5	TSL:5	c.990+2081G>A		intron	N/A	ENSP00000452765.1	H0YKE0

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57737 AN: 151866 Hom.: 12357 Cov.: 32

Gnomad AFR AF: 0.208

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.371

Gnomad ASJ AF: 0.627

Gnomad EAS AF: 0.202

Gnomad SAS AF: 0.460

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.585

Gnomad NFE AF: 0.487

Gnomad OTH AF: 0.424

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

GnomAD4 genome AF: 0.380 AC: 57724 AN: 151986 Hom.: 12351 Cov.: 32 AF XY: 0.373 AC XY: 27680 AN XY: 74290

African (AFR) AF: 0.208 AC: 8620 AN: 41476

American (AMR) AF: 0.370 AC: 5651 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.627 AC: 2170 AN: 3462

East Asian (EAS) AF: 0.202 AC: 1043 AN: 5158

South Asian (SAS) AF: 0.461 AC: 2221 AN: 4818

European-Finnish (FIN) AF: 0.317 AC: 3350 AN: 10556

Middle Eastern (MID) AF: 0.602 AC: 177 AN: 294

European-Non Finnish (NFE) AF: 0.487 AC: 33059 AN: 67942

Other (OTH) AF: 0.420 AC: 888 AN: 2112

Alfa AF: 0.459 Hom.: 21430

Bravo AF: 0.372

Asia WGS AF: 0.305 AC: 1058 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	6.6
DANN	Benign	0.51
PhyloP100		-0.20
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: rs690054; hg19: chr15-54000973;