Variant 15-53514474-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 2P and 10B. PM2BP4_StrongBP6_ModerateBS1

The NM_182758.4(WDR72):c.*3225T>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000486 in 152,284 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)

Consequence

WDR72
NM_182758.4 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.737

Variant links:

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 links:

LOC105370826 (HGNC:):

LOC105370826 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.78).

BP6

Variant 15-53514474-A-C is Benign according to our data. Variant chr15-53514474-A-C is described in ClinVar as [Benign]. Clinvar id is 884439.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000486 (74/152284) while in subpopulation AFR AF= 0.00164 (68/41552). AF 95% confidence interval is 0.00132. There are 0 homozygotes in gnomad4. There are 34 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR72	NM_182758.4 link	c.*3225T>G		3_prime_UTR_variant	Exon 20 of 20	ENST00000360509.10	NP_877435.3	Q3MJ13

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
WDR72	ENST00000360509 link	c.*3225T>G	3_prime_UTR_variant	Exon 20 of 20	1	NM_182758.4	ENSP00000353699.5	Q3MJ13
WDR72	ENST00000396328 link	c.*3225T>G	3_prime_UTR_variant	Exon 20 of 20	1		ENSP00000379619.1	Q3MJ13
WDR72	ENST00000567224.1 link	n.3600T>G	non_coding_transcript_exon_variant	Exon 3 of 3	1
WDR72	ENST00000614174.4 link	c.*3225T>G	3_prime_UTR_variant	Exon 3 of 3	2		ENSP00000477754.1	A0A087WTC3

Frequencies

GnomAD3 genomes

AF:

0.000460

AC:

AN:

152166

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000654

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.000955

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.000486

AC:

AN:

152284

Hom.:

Cov.:

AF XY:

0.000457

AC XY:

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.00164

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000408

Hom.:

Bravo

AF:

0.000491

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Amelogenesis imperfecta hypomaturation type 2A3

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.78

CADD

Benign

4.8

DANN

Benign

0.82

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over