15-84643406-G-C

Variant names:

• chr15-84643406-G-C
• rs510875
• ENST00000348993.10:n.4914G>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_032856.5(WDR73):​c.*64C>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 0.802 in 1,524,954 control chromosomes in the GnomAD database, including 494,972 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.73 (41834 hom., cov: 33)
  • Exomes 𝑓: 0.81 (453138 hom.)
• Consequence: WDR73 NM_032856.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.00800
• Publications: 10 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 15-84643406-G-C is Benign according to our data. Variant chr15-84643406-G-C is described in ClinVar as [Benign]. Clinvar id is 1256945.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.827 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR73	NM_032856.5	c.*64C>G		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.*64C>G		3_prime_UTR_variant	Exon 8 of 8	1	NM_032856.5	ENSP00000387982.3

Frequencies

GnomAD3 genomes AF: 0.733 AC: 111461 AN: 152038 Hom.: 41831 Cov.: 33

Gnomad AFR AF: 0.587

Gnomad AMI AF: 0.860

Gnomad AMR AF: 0.677

Gnomad ASJ AF: 0.820

Gnomad EAS AF: 0.580

Gnomad SAS AF: 0.701

Gnomad FIN AF: 0.796

Gnomad MID AF: 0.722

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.733

GnomAD4 exome AF: 0.809 AC: 1111129 AN: 1372798 Hom.: 453138 Cov.: 31 AF XY: 0.808 AC XY: 544722 AN XY: 674252

African (AFR) AF: 0.576 AC: 17958 AN: 31170

American (AMR) AF: 0.632 AC: 21712 AN: 34354

Ashkenazi Jewish (ASJ) AF: 0.830 AC: 19342 AN: 23308

East Asian (EAS) AF: 0.626 AC: 22283 AN: 35586

South Asian (SAS) AF: 0.716 AC: 53307 AN: 74474

European-Finnish (FIN) AF: 0.809 AC: 38586 AN: 47710

Middle Eastern (MID) AF: 0.775 AC: 3091 AN: 3990

European-Non Finnish (NFE) AF: 0.836 AC: 890228 AN: 1065372

Other (OTH) AF: 0.785 AC: 44622 AN: 56834

GnomAD4 genome AF: 0.733 AC: 111507 AN: 152156 Hom.: 41834 Cov.: 33 AF XY: 0.727 AC XY: 54088 AN XY: 74390

African (AFR) AF: 0.587 AC: 24322 AN: 41462

American (AMR) AF: 0.676 AC: 10337 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.820 AC: 2846 AN: 3470

East Asian (EAS) AF: 0.580 AC: 3000 AN: 5174

South Asian (SAS) AF: 0.700 AC: 3382 AN: 4828

European-Finnish (FIN) AF: 0.796 AC: 8441 AN: 10598

Middle Eastern (MID) AF: 0.721 AC: 212 AN: 294

European-Non Finnish (NFE) AF: 0.833 AC: 56632 AN: 68024

Other (OTH) AF: 0.734 AC: 1551 AN: 2112

Alfa AF: 0.780 Hom.: 5819

Bravo AF: 0.717

Asia WGS AF: 0.639 AC: 2222 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

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	-0.88
CADD	Benign	1.6
DANN	Benign	0.74
PhyloP100		0.0080
Mutation Taster		=100/0	polymorphism (auto)

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: rs510875; hg19: chr15-85186637; COSMIC: COSV62411070; COSMIC: COSV62411070;