Variant 15-84643346-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_032856.5(WDR73):c.*124G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.235 in 1,218,342 control chromosomes in the GnomAD database, including 35,480 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.20 ( 3563 hom., cov: 32)

Exomes 𝑓: 0.24 ( 31917 hom. )

Consequence

WDR73
NM_032856.5 3_prime_UTR

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -1.68

Variant links:

Genes affected

WDR73 (HGNC:25928): (WD repeat domain 73) The protein encoded by this gene is thought to contain multiple WD40 repeats. WD40 repeats are motifs that contain 40-60 amino acids, and usually end with Trp-Asp (WD). This protein is found in the cytoplasm during interphase, but accumulates at the spindle poles and astral microtubules during mitosis. Reduced expression of this gene results in abnormalities in the size and morphology of the nucleus. Mutations in this gene have been associated with Galloway-Mowat syndrome PMID: 25466283), which is a rare autosomal recessive disorder that affects both the central nervous system and kidneys. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Feb 2015]

WDR73 links:

ENSG00000291159 (HGNC:):

ENSG00000291159 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 15-84643346-C-T is Benign according to our data. Variant chr15-84643346-C-T is described in ClinVar as [Benign]. Clinvar id is 1226394.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.259 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR73	NM_032856.5 linkuse as main transcript	c.*124G>A		3_prime_UTR_variant	8/8	ENST00000434634.7	NP_116245.2	Q6P4I2Q6PJL8Q5RKY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR73	ENST00000434634 linkuse as main transcript	c.*124G>A		3_prime_UTR_variant	8/8	1	NM_032856.5	ENSP00000387982.3		Q6P4I2

Frequencies

GnomAD3 genomes

AF:

0.205

AC:

31119

AN:

152028

Hom.:

3562

Cov.:

show subpopulations

Gnomad AFR

AF:

0.118

Gnomad AMI

AF:

0.460

Gnomad AMR

AF:

0.198

Gnomad ASJ

AF:

0.257

Gnomad EAS

AF:

0.108

Gnomad SAS

AF:

0.143

Gnomad FIN

AF:

0.214

Gnomad MID

AF:

0.307

Gnomad NFE

AF:

0.263

Gnomad OTH

AF:

0.214

GnomAD4 exome

AF:

0.239

AC:

255090

AN:

1066196

Hom.:

31917

Cov.:

AF XY:

0.239

AC XY:

125603

AN XY:

526590

show subpopulations

Gnomad4 AFR exome

AF:

0.116

Gnomad4 AMR exome

AF:

0.185

Gnomad4 ASJ exome

AF:

0.258

Gnomad4 EAS exome

AF:

0.0974

Gnomad4 SAS exome

AF:

0.166

Gnomad4 FIN exome

AF:

0.208

Gnomad4 NFE exome

AF:

0.257

Gnomad4 OTH exome

AF:

0.224

GnomAD4 genome

AF:

0.205

AC:

31122

AN:

152146

Hom.:

3563

Cov.:

AF XY:

0.201

AC XY:

14922

AN XY:

74390

show subpopulations

Gnomad4 AFR

AF:

0.118

Gnomad4 AMR

AF:

0.198

Gnomad4 ASJ

AF:

0.257

Gnomad4 EAS

AF:

0.107

Gnomad4 SAS

AF:

0.144

Gnomad4 FIN

AF:

0.214

Gnomad4 NFE

AF:

0.263

Gnomad4 OTH

AF:

0.211

Alfa

AF:

0.259

Hom.:

5447

Bravo

AF:

0.203

Asia WGS

AF:

0.150

AC:

523

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 20, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.23

DANN

Benign

0.54

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