rs34069323

Positions:

• chr15-84644014-T-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_032856.5(WDR73):​c.884-291A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00738 in 319,500 control chromosomes in the GnomAD database, including 18 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 0.0062 (4 hom., cov: 32)
  • Exomes 𝑓: 0.0085 (14 hom.)
• Consequence: WDR73 NM_032856.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.81

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]

ENSG00000291159 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BS1: Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00619 (943/152318) while in subpopulation SAS AF= 0.0114 (55/4822). AF 95% confidence interval is 0.0091. There are 4 homozygotes in gnomad4. There are 386 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
WDR73	NM_032856.5	c.884-291A>G		intron_variant		ENST00000434634.7	NP_116245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR73	ENST00000434634.7	c.884-291A>G		intron_variant		1	NM_032856.5	ENSP00000387982.3

Frequencies

GnomAD3 genomes AF: 0.00619 AC: 942 AN: 152200 Hom.: 4 Cov.: 32

Gnomad AFR AF: 0.00229

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00563

Gnomad ASJ AF: 0.00404

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.0114

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00971

Gnomad OTH AF: 0.00813

GnomAD4 exome AF: 0.00846 AC: 1415 AN: 167182 Hom.: 14 Cov.: 0 AF XY: 0.00877 AC XY: 788 AN XY: 89888

Gnomad4 AFR exome AF: 0.000905

Gnomad4 AMR exome AF: 0.00496

Gnomad4 ASJ exome AF: 0.00470

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0137

Gnomad4 FIN exome AF: 0.00165

Gnomad4 NFE exome AF: 0.00917

Gnomad4 OTH exome AF: 0.00685

GnomAD4 genome AF: 0.00619 AC: 943 AN: 152318 Hom.: 4 Cov.: 32 AF XY: 0.00518 AC XY: 386 AN XY: 74488

Gnomad4 AFR AF: 0.00229

Gnomad4 AMR AF: 0.00562

Gnomad4 ASJ AF: 0.00404

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0114

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.00972

Gnomad4 OTH AF: 0.00804

Alfa AF: 0.00818 Hom.: 0

Bravo AF: 0.00665

Asia WGS AF: 0.00202 AC: 7 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.55
DANN	Benign	0.64

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs34069323; hg19: chr15-85187245;