15-53716598-T-C

Variant names:

• chr15-53716598-T-C
• rs690337
• NM_182758.4:c.339+9A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_182758.4(WDR72):​c.339+9A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.753 in 1,567,246 control chromosomes in the GnomAD database, including 446,002 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.74 (41806 hom., cov: 33)
  • Exomes 𝑓: 0.75 (404196 hom.)
• Consequence: WDR72 NM_182758.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: -1.45
• Publications: 11 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 15-53716598-T-C is Benign according to our data. Variant chr15-53716598-T-C is described in ClinVar as Benign. ClinVar VariationId is 263002.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.776 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	NM_182758.4	MANE Select	c.339+9A>G		intron	N/A	NP_877435.3
	WDR72	NR_102334.2		n.579+9A>G		intron	N/A

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR72	ENST00000360509.10	TSL:1 MANE Select	c.339+9A>G		intron	N/A	ENSP00000353699.5
	WDR72	ENST00000396328.5	TSL:1	c.339+9A>G		intron	N/A	ENSP00000379619.1
	WDR72	ENST00000559418.5	TSL:5	c.339+9A>G		intron	N/A	ENSP00000452765.1

Frequencies

GnomAD3 genomes AF: 0.741 AC: 112577 AN: 151994 Hom.: 41787 Cov.: 33

Gnomad AFR AF: 0.729

Gnomad AMI AF: 0.816

Gnomad AMR AF: 0.734

Gnomad ASJ AF: 0.784

Gnomad EAS AF: 0.730

Gnomad SAS AF: 0.796

Gnomad FIN AF: 0.647

Gnomad MID AF: 0.801

Gnomad NFE AF: 0.757

Gnomad OTH AF: 0.740

GnomAD2 exomes AF: 0.745 AC: 187005 AN: 251122 AF XY: 0.748

Gnomad AFR exome AF: 0.729

Gnomad AMR exome AF: 0.720

Gnomad ASJ exome AF: 0.771

Gnomad EAS exome AF: 0.740

Gnomad FIN exome AF: 0.661

Gnomad NFE exome AF: 0.754

Gnomad OTH exome AF: 0.746

GnomAD4 exome AF: 0.755 AC: 1067939 AN: 1415134 Hom.: 404196 Cov.: 25 AF XY: 0.756 AC XY: 534555 AN XY: 706786

African (AFR) AF: 0.728 AC: 23715 AN: 32574

American (AMR) AF: 0.723 AC: 32293 AN: 44640

Ashkenazi Jewish (ASJ) AF: 0.764 AC: 19721 AN: 25820

East Asian (EAS) AF: 0.741 AC: 29244 AN: 39464

South Asian (SAS) AF: 0.797 AC: 67995 AN: 85312

European-Finnish (FIN) AF: 0.668 AC: 35622 AN: 53346

Middle Eastern (MID) AF: 0.778 AC: 4429 AN: 5690

European-Non Finnish (NFE) AF: 0.758 AC: 810224 AN: 1069404

Other (OTH) AF: 0.759 AC: 44696 AN: 58884

GnomAD4 genome AF: 0.741 AC: 112648 AN: 152112 Hom.: 41806 Cov.: 33 AF XY: 0.737 AC XY: 54790 AN XY: 74358

African (AFR) AF: 0.729 AC: 30242 AN: 41504

American (AMR) AF: 0.734 AC: 11220 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.784 AC: 2717 AN: 3466

East Asian (EAS) AF: 0.730 AC: 3760 AN: 5154

South Asian (SAS) AF: 0.797 AC: 3840 AN: 4816

European-Finnish (FIN) AF: 0.647 AC: 6846 AN: 10578

Middle Eastern (MID) AF: 0.796 AC: 234 AN: 294

European-Non Finnish (NFE) AF: 0.757 AC: 51472 AN: 67990

Other (OTH) AF: 0.745 AC: 1574 AN: 2114

Alfa AF: 0.754 Hom.: 194821

Bravo AF: 0.745

Asia WGS AF: 0.751 AC: 2609 AN: 3476

EpiCase AF: 0.761

EpiControl AF: 0.763

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Amelogenesis imperfecta hypomaturation type 2A3 (1)
-	-	1	Amelogenesis Imperfecta, Recessive (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.038
DANN	Benign	0.61
PhyloP100		-1.4
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs690337; hg19: chr15-54008795;