15-53759056-C-T

Variant names:

• chr15-53759056-C-T
• rs7183817
• NM_182758.4:c.-13+577G>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.-13+577G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.311 in 151,788 control chromosomes in the GnomAD database, including 8,000 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 0.31 (8000 hom., cov: 29)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.701
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.444 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4	c.-13+577G>A		intron_variant	Intron 1 of 19	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.-13+577G>A		intron_variant	Intron 1 of 19	1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328.5	c.-13+3595G>A		intron_variant	Intron 1 of 19	1		ENSP00000379619.1
WDR72	ENST00000557913.5	c.-13+531G>A		intron_variant	Intron 1 of 19	5		ENSP00000453378.1
WDR72	ENST00000560036.1	c.-164+245G>A		intron_variant	Intron 1 of 15	2		ENSP00000453813.1

Frequencies

GnomAD3 genomes AF: 0.311 AC: 47203 AN: 151672 Hom.: 7983 Cov.: 29

Gnomad AFR AF: 0.176

Gnomad AMI AF: 0.349

Gnomad AMR AF: 0.378

Gnomad ASJ AF: 0.297

Gnomad EAS AF: 0.437

Gnomad SAS AF: 0.461

Gnomad FIN AF: 0.392

Gnomad MID AF: 0.269

Gnomad NFE AF: 0.346

Gnomad OTH AF: 0.301

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

GnomAD4 genome AF: 0.311 AC: 47240 AN: 151788 Hom.: 8000 Cov.: 29 AF XY: 0.319 AC XY: 23646 AN XY: 74124

African (AFR) AF: 0.176 AC: 7300 AN: 41402

American (AMR) AF: 0.378 AC: 5767 AN: 15256

Ashkenazi Jewish (ASJ) AF: 0.297 AC: 1032 AN: 3470

East Asian (EAS) AF: 0.437 AC: 2237 AN: 5118

South Asian (SAS) AF: 0.460 AC: 2210 AN: 4802

European-Finnish (FIN) AF: 0.392 AC: 4120 AN: 10520

Middle Eastern (MID) AF: 0.269 AC: 79 AN: 294

European-Non Finnish (NFE) AF: 0.346 AC: 23528 AN: 67916

Other (OTH) AF: 0.309 AC: 649 AN: 2100

Alfa AF: 0.335 Hom.: 12294

Bravo AF: 0.302

Asia WGS AF: 0.446 AC: 1553 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	2.2
DANN	Benign	0.55
PhyloP100		-0.70
PromoterAI		-0.0062	Neutral
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: rs7183817; hg19: chr15-54051253;