chr15-53655665-A-G

Position:

• chr15-53655665-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000360509.10(WDR72):​c.1962+9907T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0733 in 152,114 control chromosomes in the GnomAD database, including 1,006 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 0.073 (1006 hom., cov: 32)
• Consequence: WDR72 ENST00000360509.10 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.379

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.21 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4	c.1962+9907T>C		intron_variant		ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509.10	c.1962+9907T>C		intron_variant		1	NM_182758.4	ENSP00000353699	P4

Frequencies

GnomAD3 genomes AF: 0.0732 AC: 11131 AN: 151996 Hom.: 1003 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0314

Gnomad ASJ AF: 0.000865

Gnomad EAS AF: 0.0694

Gnomad SAS AF: 0.0475

Gnomad FIN AF: 0.0198

Gnomad MID AF: 0.0190

Gnomad NFE AF: 0.0131

Gnomad OTH AF: 0.0521

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

GnomAD4 genome AF: 0.0733 AC: 11157 AN: 152114 Hom.: 1006 Cov.: 32 AF XY: 0.0734 AC XY: 5462 AN XY: 74382

Gnomad4 AFR AF: 0.214

Gnomad4 AMR AF: 0.0314

Gnomad4 ASJ AF: 0.000865

Gnomad4 EAS AF: 0.0692

Gnomad4 SAS AF: 0.0471

Gnomad4 FIN AF: 0.0198

Gnomad4 NFE AF: 0.0131

Gnomad4 OTH AF: 0.0567

Alfa AF: 0.0480 Hom.: 89

Bravo AF: 0.0792

Asia WGS AF: 0.0680 AC: 236 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	4.7
DANN	Benign	0.47

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: rs1621807; hg19: chr15-53947862;