15-84643298-T-A

Variant names:

• chr15-84643298-T-A
• rs114735678
• ENST00000348993.10:n.4806T>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_032856.5(WDR73):​c.*172A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00474 in 735,626 control chromosomes in the GnomAD database, including 92 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (64 hom., cov: 32)
  • Exomes 𝑓: 0.0020 (28 hom.)
• Consequence: WDR73 NM_032856.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.219
• Publications: 0 publications found

Genes affected

ENSG00000291159 (HGNC:):

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 Gene-Disease associations (from GenCC):

• Galloway-Mowat syndrome 1

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• CAMOS syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Galloway-Mowat syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 15-84643298-T-A is Benign according to our data. Variant chr15-84643298-T-A is described in ClinVar as [Benign]. Clinvar id is 1252141.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0153 (2325/152340) while in subpopulation AFR AF = 0.0507 (2108/41572). AF 95% confidence interval is 0.0489. There are 64 homozygotes in GnomAd4. There are 1082 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 64 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR73	NM_032856.5	c.*172A>T		3_prime_UTR_variant	Exon 8 of 8	ENST00000434634.7	NP_116245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR73	ENST00000434634.7	c.*172A>T		3_prime_UTR_variant	Exon 8 of 8	1	NM_032856.5	ENSP00000387982.3

Frequencies

GnomAD3 genomes AF: 0.0153 AC: 2326 AN: 152222 Hom.: 63 Cov.: 32

Gnomad AFR AF: 0.0509

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0106

Gnomad ASJ AF: 0.00461

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.0134

GnomAD4 exome AF: 0.00199 AC: 1162 AN: 583286 Hom.: 28 Cov.: 8 AF XY: 0.00168 AC XY: 507 AN XY: 301284

African (AFR) AF: 0.0500 AC: 743 AN: 14860

American (AMR) AF: 0.00550 AC: 104 AN: 18904

Ashkenazi Jewish (ASJ) AF: 0.00488 AC: 71 AN: 14556

East Asian (EAS) AF: 0.00 AC: 0 AN: 31754

South Asian (SAS) AF: 0.0000207 AC: 1 AN: 48236

European-Finnish (FIN) AF: 0.0000322 AC: 1 AN: 31008

Middle Eastern (MID) AF: 0.00223 AC: 5 AN: 2238

European-Non Finnish (NFE) AF: 0.000161 AC: 63 AN: 391282

Other (OTH) AF: 0.00571 AC: 174 AN: 30448

GnomAD4 genome AF: 0.0153 AC: 2325 AN: 152340 Hom.: 64 Cov.: 32 AF XY: 0.0145 AC XY: 1082 AN XY: 74504

African (AFR) AF: 0.0507 AC: 2108 AN: 41572

American (AMR) AF: 0.0106 AC: 162 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00461 AC: 16 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5192

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10630

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68028

Other (OTH) AF: 0.0132 AC: 28 AN: 2116

Alfa AF: 0.0120 Hom.: 6

Bravo AF: 0.0177

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Mar 02, 2020

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.78
DANN	Benign	0.67
PhyloP100		-0.22
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs114735678; hg19: chr15-85186529;