Genetic Variant WDR73:p.Arg378Gly (chr15-84643475-G-C) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_032856.5(WDR73):c.1132C>G(p.Arg378Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000715 in 1,399,542 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R378H) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

WDR73
NM_032856.5 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.55

Publications

2 publications found

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 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

WDR73 links:

ENSG00000291159 (HGNC:):

ENSG00000291159 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.04973522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR73	NM_032856.5 link	c.1132C>G	p.Arg378Gly	missense_variant	Exon 8 of 8	ENST00000434634.7	NP_116245.2	Q6P4I2Q6PJL8Q5RKY8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR73	ENST00000434634.7 link	c.1132C>G	p.Arg378Gly	missense_variant	Exon 8 of 8	1	NM_032856.5	ENSP00000387982.3		Q6P4I2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.15e-7

AC:

AN:

1399542

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

690748

show subpopulations

African (AFR)

AF:

0.0000314

AC:

AN:

31886

American (AMR)

AF:

0.00

AC:

AN:

35892

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25180

East Asian (EAS)

AF:

0.00

AC:

AN:

36094

South Asian (SAS)

AF:

0.00

AC:

AN:

79438

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49768

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5204

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1078034

Other (OTH)

AF:

0.00

AC:

AN:

58046

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.092

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.61

CADD

Benign

0.30

(source)

DANN

Benign

0.91

DEOGEN2

Benign

0.0022

Eigen

Benign

-1.8

Eigen_PC

Benign

-1.9

FATHMM_MKL

Benign

0.083

LIST_S2

Benign

0.28

M_CAP

Benign

0.020

MetaRNN

Benign

0.050

MetaSVM

Benign

-0.95

MutationAssessor

Benign

0.0

PhyloP100

-1.6

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.88

REVEL

Benign

0.089

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

0.0

Vest4

0.048

MutPred

0.55

Gain of disorder (P = 0.1048);

MVP

0.081

MPC

0.10

ClinPred

0.18

GERP RS

-12

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.065

gMVP

0.33

Mutation Taster

=98/2

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over