Variant 6-169582922-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_182552.5(WDR27):c.2437G>C(p.Glu813Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000347 in 1,613,734 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/18 in silico tools predict 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. E813G) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00021 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

WDR27
NM_182552.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.09

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 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10191235).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR27	NM_182552.5 linkuse as main transcript	c.2437G>C	p.Glu813Gln	missense_variant	24/26	ENST00000448612.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR27	ENST00000448612.6 linkuse as main transcript	c.2437G>C	p.Glu813Gln	missense_variant	24/26	1	NM_182552.5	A2	A2RRH5-4

Frequencies

GnomAD3 genomes

AF:

0.000210

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000724

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000442

AC:

AN:

248832

Hom.:

AF XY:

0.0000444

AC XY:

AN XY:

135002

show subpopulations

Gnomad AFR exome

AF:

0.000648

Gnomad AMR exome

AF:

0.0000290

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS 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:

0.0000164

AC:

AN:

1461572

Hom.:

Cov.:

AF XY:

0.0000124

AC XY:

AN XY:

727044

show subpopulations

Gnomad4 AFR exome

AF:

0.000627

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000210

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.000242

AC XY:

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.000724

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000223

ESP6500AA

AF:

0.000719

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000496

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

Jan 26, 2022

The c.2437G>C (p.E813Q) alteration is located in exon 24 (coding exon 23) of the WDR27 gene. This alteration results from a G to C substitution at nucleotide position 2437, causing the glutamic acid (E) at amino acid position 813 to be replaced by a glutamine (Q). 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

-0.42

BayesDel_noAF

Benign

-0.46

CADD

Benign

DANN

Uncertain

1.0

Eigen

Benign

0.079

Eigen_PC

Benign

-0.029

FATHMM_MKL

Benign

0.48

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0042

MetaRNN

Benign

0.10

T;T

MetaSVM

Benign

-0.93

MutationTaster

Benign

1.0

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-2.2

N;N

REVEL

Benign

0.18

Sift

Uncertain

0.028

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

0.99

.;D

Vest4

0.45

MVP

0.11

MPC

0.15

ClinPred

0.087

GERP RS

4.5

gMVP

0.23

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.030

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