Genetic Variant WDR73:c.*124G>C (chr15-84643346-C-G) – 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.*124G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000936 in 1,068,168 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 9.4e-7 ( 0 hom. )

Consequence

WDR73
NM_032856.5 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.68

Publications

0 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:58684):

ENSG00000291159 links:

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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 (BayesDel_noAF=-0.88).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_032856.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR73	NM_032856.5	MANE Select	c.*124G>C	3_prime_UTR	Exon 8 of 8	NP_116245.2	Q6P4I2
WDR73	NR_130944.2		n.1804G>C	non_coding_transcript_exon	Exon 7 of 7
WDR73	NR_130945.2		n.1383G>C	non_coding_transcript_exon	Exon 9 of 9

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
WDR73	ENST00000434634.7	TSL:1 MANE Select	c.*124G>C	3_prime_UTR	Exon 8 of 8	ENSP00000387982.3	Q6P4I2
ENSG00000291159	ENST00000348993.10	TSL:1	n.4854C>G	non_coding_transcript_exon	Exon 4 of 4
WDR73	ENST00000398528.7	TSL:1	n.1337G>C	non_coding_transcript_exon	Exon 8 of 8

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.36e-7

AC:

AN:

1068168

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

527530

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23820

American (AMR)

AF:

0.00

AC:

AN:

21568

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

17852

East Asian (EAS)

AF:

0.00

AC:

AN:

33860

South Asian (SAS)

AF:

0.00

AC:

AN:

58748

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39346

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3178

European-Non Finnish (NFE)

AF:

0.00000121

AC:

AN:

823584

Other (OTH)

AF:

0.00

AC:

AN:

46212

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.88

CADD

Benign

0.20

(source)

DANN

Benign

0.43

PhyloP100

-1.7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over