NM_001347217.2:c.892G>A

Variant names:

• chrX-48601844-G-A
• rs201415075
• NM_001347217.2:c.892G>A

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001347217.2(WDR13):​c.892G>A​(p.Gly298Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000184 in 1,089,833 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. 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. G298W) has been classified as Likely benign.

• Frequency:
  • Genomes: not found (cov: 24)
  • Exomes 𝑓: 0.0000018 (0 hom. 1 hem.)
• Consequence: WDR13 NM_001347217.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 8.64
• Publications: 0 publications found

Genes affected

WDR13 (HGNC:14352): (WD repeat domain 13) This gene encodes a member of the WD repeat protein family. WD repeats are minimally conserved regions of approximately 40 amino acids typically bracketed by Gly-His and Trp-Asp (GH-WD), which may facilitate formation of heterotrimeric or multiprotein complexes. Members of this family are involved in a variety of cellular processes, including cell cycle progression, signal transduction, apoptosis, and gene regulation. A similar protein in mouse is thought to be a negative regulator of the pancreatic beta cell proliferation. Mice lacking this gene exhibit increased pancreatic islet mass and higher serum insulin levels, and are mildly obese. [provided by RefSeq, Nov 2016]

WDR13 Gene-Disease associations (from GenCC):

• intellectual disability

  Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001347217.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR13	NM_001347217.2	MANE Select	c.892G>A	p.Gly298Arg	missense	Exon 7 of 10	NP_001334146.1	Q9H1Z4-1
	WDR13	NM_017883.6		c.892G>A	p.Gly298Arg	missense	Exon 6 of 9	NP_060353.2
	WDR13	NM_001166426.3		c.616G>A	p.Gly206Arg	missense	Exon 5 of 8	NP_001159898.1	Q9H1Z4-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR13	ENST00000376729.10	TSL:5 MANE Select	c.892G>A	p.Gly298Arg	missense	Exon 7 of 10	ENSP00000365919.5	Q9H1Z4-1
	WDR13	ENST00000218056.9	TSL:1	c.892G>A	p.Gly298Arg	missense	Exon 6 of 9	ENSP00000218056.5	Q9H1Z4-1
	WDR13	ENST00000479279.5	TSL:1	n.1759G>A		non_coding_transcript_exon	Exon 5 of 8

Frequencies

GnomAD3 genomes Cov.: 24

GnomAD2 exomes AF: 0.00000581 AC: 1 AN: 172041 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000184 AC: 2 AN: 1089833 Hom.: 0 Cov.: 31 AF XY: 0.00000280 AC XY: 1 AN XY: 356857

African (AFR) AF: 0.00 AC: 0 AN: 26209

American (AMR) AF: 0.00 AC: 0 AN: 34178

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18840

East Asian (EAS) AF: 0.00 AC: 0 AN: 30101

South Asian (SAS) AF: 0.0000378 AC: 2 AN: 52852

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 40255

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4084

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 837563

Other (OTH) AF: 0.00 AC: 0 AN: 45751

GnomAD4 genome Cov.: 24

ExAC AF: 0.00000824 AC: 1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.33
CADD	Pathogenic	28
DANN	Pathogenic	1.0
DEOGEN2	Benign	0.11	T
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.96	D
M_CAP	Uncertain	0.22	D
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-0.54	T
PhyloP100		8.6
PrimateAI	Pathogenic	0.86	D
PROVEAN	Pathogenic	-4.5	D
REVEL	Uncertain	0.47
Sift	Uncertain	0.0030	D
Sift4G	Uncertain	0.0030	D
Vest4		0.42
MutPred		0.26		Gain of MoRF binding (P = 0.0432)
MVP		0.83
MPC		2.3
ClinPred		0.81	D
GERP RS		5.4
gMVP		0.82
Mutation Taster		=75/25	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs201415075; hg19: chrX-48460232;