Variant 6-169632976-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_182552.5(WDR27):c.2194C>T(p.Arg732Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000847 in 1,594,132 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R732Q) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00032 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000060 ( 0 hom. )

Consequence

WDR27
NM_182552.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.44

Variant links:

Genes affected

WDR27 (HGNC:21248): (WD repeat domain 27) This gene encodes a protein with multiple WD repeats. Proteins with these repeats may form scaffolds for protein-protein interaction and play key roles in cell signalling. Alternative splicing results in multiple transcript variants, but the full-length structure of some of these variants cannot be determined. [provided by RefSeq, Nov 2015]

WDR27 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.26557776).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR27	NM_182552.5 linkuse as main transcript	c.2194C>T	p.Arg732Trp	missense_variant	21/26	ENST00000448612.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR27	ENST00000448612.6 linkuse as main transcript	c.2194C>T	p.Arg732Trp	missense_variant	21/26	1	NM_182552.5	A2	A2RRH5-4

Frequencies

GnomAD3 genomes

AF:

0.000322

AC:

AN:

152212

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.000955

GnomAD3 exomes

AF:

0.0000926

AC:

AN:

248472

Hom.:

AF XY:

0.0000742

AC XY:

AN XY:

134818

show subpopulations

Gnomad AFR exome

AF:

0.00110

Gnomad AMR exome

AF:

0.0000584

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000557

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000266

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000596

AC:

AN:

1441802

Hom.:

Cov.:

AF XY:

0.0000505

AC XY:

AN XY:

712736

show subpopulations

Gnomad4 AFR exome

AF:

0.000602

Gnomad4 AMR exome

AF:

0.0000675

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000235

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000538

Gnomad4 OTH exome

AF:

0.0000337

GnomAD4 genome

AF:

0.000322

AC:

AN:

152330

Hom.:

Cov.:

AF XY:

0.000309

AC XY:

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000962

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.000945

Alfa

AF:

0.000150

Hom.:

Bravo

AF:

0.000332

ESP6500AA

AF:

0.000258

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000993

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Apr 27, 2023

The c.2194C>T (p.R732W) alteration is located in exon 21 (coding exon 20) of the WDR27 gene. This alteration results from a C to T substitution at nucleotide position 2194, causing the arginine (R) at amino acid position 732 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.24

BayesDel_noAF

Benign

-0.17

CADD

Benign

DANN

Uncertain

1.0

Eigen

Uncertain

0.20

Eigen_PC

Benign

0.0035

FATHMM_MKL

Benign

0.35

LIST_S2

Uncertain

0.95

D;D

M_CAP

Benign

0.019

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.83

MutationTaster

Benign

0.98

N;N;N

PrimateAI

Benign

0.48

PROVEAN

Pathogenic

-6.9

D;D

REVEL

Benign

0.20

Sift

Pathogenic

0.0

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.60

MVP

0.21

MPC

0.080

ClinPred

0.88

GERP RS

0.40

gMVP

0.59

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over