15-84652428-T-C

Variant names:

• chr15-84652428-T-C
• rs7180849
• NM_032856.5:c.198+286A>G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_032856.5(WDR73):​c.198+286A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.872 in 152,150 control chromosomes in the GnomAD database, including 58,089 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.87 (58089 hom., cov: 31)
• Consequence: WDR73 NM_032856.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.155

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]

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BP6: Variant 15-84652428-T-C is Benign according to our data. Variant chr15-84652428-T-C is described in ClinVar as [Benign]. Clinvar id is 1258449.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.943 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR73	NM_032856.5	c.198+286A>G		intron_variant	Intron 3 of 7	ENST00000434634.7	NP_116245.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR73	ENST00000434634.7	c.198+286A>G		intron_variant	Intron 3 of 7	1	NM_032856.5	ENSP00000387982.3

Frequencies

GnomAD3 genomes AF: 0.872 AC: 132567 AN: 152032 Hom.: 58026 Cov.: 31

Gnomad AFR AF: 0.951

Gnomad AMI AF: 0.843

Gnomad AMR AF: 0.883

Gnomad ASJ AF: 0.881

Gnomad EAS AF: 0.944

Gnomad SAS AF: 0.803

Gnomad FIN AF: 0.795

Gnomad MID AF: 0.861

Gnomad NFE AF: 0.833

Gnomad OTH AF: 0.862

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.872 AC: 132686 AN: 152150 Hom.: 58089 Cov.: 31 AF XY: 0.870 AC XY: 64680 AN XY: 74354

Gnomad4 AFR AF: 0.951

Gnomad4 AMR AF: 0.883

Gnomad4 ASJ AF: 0.881

Gnomad4 EAS AF: 0.944

Gnomad4 SAS AF: 0.804

Gnomad4 FIN AF: 0.795

Gnomad4 NFE AF: 0.833

Gnomad4 OTH AF: 0.857

Alfa AF: 0.823 Hom.: 2957

Bravo AF: 0.883

Asia WGS AF: 0.881 AC: 3063 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.29

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

LitVar

Other links and lift over

dbSNP: rs7180849; hg19: chr15-85195659;