chr15-53699950-G-GA

Position:

• chr15-53699950-G-GA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_182758.4(WDR72):​c.1570-6dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 1,613,998 control chromosomes in the GnomAD database, including 28 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0015 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0011 (24 hom.)
• Consequence: WDR72 NM_182758.4 splice_region, intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.365

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 15-53699950-G-GA is Benign according to our data. Variant chr15-53699950-G-GA is described in ClinVar as [Likely_benign]. Clinvar id is 376835.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00154 (235/152224) while in subpopulation AMR AF= 0.0122 (186/15286). AF 95% confidence interval is 0.0107. There are 4 homozygotes in gnomad4. There are 119 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4	c.1570-6dupT		splice_region_variant, intron_variant		ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.1570-6dupT		splice_region_variant, intron_variant		1	NM_182758.4	ENSP00000353699.5

Frequencies

GnomAD3 genomes AF: 0.00154 AC: 234 AN: 152106 Hom.: 3 Cov.: 32

Gnomad AFR AF: 0.000434

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0121

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00443

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000882

Gnomad OTH AF: 0.000957

GnomAD3 exomes AF: 0.00459 AC: 1153 AN: 251192 Hom.: 22 AF XY: 0.00354 AC XY: 481 AN XY: 135822

Gnomad AFR exome AF: 0.000495

Gnomad AMR exome AF: 0.0299

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00381

Gnomad SAS exome AF: 0.000490

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000792

Gnomad OTH exome AF: 0.00294

GnomAD4 exome AF: 0.00108 AC: 1584 AN: 1461774 Hom.: 24 Cov.: 31 AF XY: 0.000930 AC XY: 676 AN XY: 727188

Gnomad4 AFR exome AF: 0.000299

Gnomad4 AMR exome AF: 0.0271

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00577

Gnomad4 SAS exome AF: 0.000290

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000630

Gnomad4 OTH exome AF: 0.000596

GnomAD4 genome AF: 0.00154 AC: 235 AN: 152224 Hom.: 4 Cov.: 32 AF XY: 0.00160 AC XY: 119 AN XY: 74432

Gnomad4 AFR AF: 0.000433

Gnomad4 AMR AF: 0.0122

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00425

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000882

Gnomad4 OTH AF: 0.000947

Bravo AF: 0.00312

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.000119

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Dec 06, 2016

- -

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs34118367; hg19: chr15-53992147;