chr15-53514535-A-G

Position:

• chr15-53514535-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_182758.4(WDR72):​c.*3164T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00698 in 152,312 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0070 (18 hom., cov: 32)
  • Failed GnomAD Quality Control
• Consequence: WDR72 NM_182758.4 3_prime_UTR
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.556

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]

LOC105370826 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BP6: Variant 15-53514535-A-G is Benign according to our data. Variant chr15-53514535-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 316497.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0644 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR72	NM_182758.4	c.*3164T>C		3_prime_UTR_variant	20/20	ENST00000360509.10	NP_877435.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR72	ENST00000360509	c.*3164T>C		3_prime_UTR_variant	20/20	1	NM_182758.4	ENSP00000353699.5
WDR72	ENST00000396328	c.*3164T>C		3_prime_UTR_variant	20/20	1		ENSP00000379619.1
WDR72	ENST00000567224.1	n.3539T>C		non_coding_transcript_exon_variant	3/3	1
WDR72	ENST00000614174.4	c.*3164T>C		3_prime_UTR_variant	3/3	2		ENSP00000477754.1

Frequencies

GnomAD3 genomes AF: 0.00693 AC: 1055 AN: 152194 Hom.: 16 Cov.: 32

Gnomad AFR AF: 0.00137

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.00569

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0700

Gnomad SAS AF: 0.0404

Gnomad FIN AF: 0.000283

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00485

Gnomad OTH AF: 0.00525

GnomAD4 exome Data not reliable, filtered out with message: AC0 AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome AF: 0.00698 AC: 1063 AN: 152312 Hom.: 18 Cov.: 32 AF XY: 0.00779 AC XY: 580 AN XY: 74486

Gnomad4 AFR AF: 0.00137

Gnomad4 AMR AF: 0.00569

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.0704

Gnomad4 SAS AF: 0.0402

Gnomad4 FIN AF: 0.000283

Gnomad4 NFE AF: 0.00485

Gnomad4 OTH AF: 0.00945

Alfa AF: 0.00460 Hom.: 0

Bravo AF: 0.00676

Asia WGS AF: 0.0470 AC: 165 AN: 3476

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Amelogenesis Imperfecta, Recessive Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.28
DANN	Benign	0.39

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: rs143400580; hg19: chr15-53806732; COSMIC: COSV64750408; COSMIC: COSV64750408;