6-169582921-T-C

Variant summary

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

The NM_182552.5(WDR27):ā€‹c.2438A>Gā€‹(p.Glu813Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000124 in 1,613,750 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 (ā˜…).

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 30)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

WDR27
NM_182552.5 missense

Scores

2
3
11

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.91
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]

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=0.35587212).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
WDR27NM_182552.5 linkuse as main transcriptc.2438A>G p.Glu813Gly missense_variant 24/26 ENST00000448612.6 NP_872358.4 A2RRH5-4

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
WDR27ENST00000448612.6 linkuse as main transcriptc.2438A>G p.Glu813Gly missense_variant 24/261 NM_182552.5 ENSP00000416289.1 A2RRH5-4
ENSG00000285733ENST00000648086.1 linkuse as main transcriptc.448A>G p.Lys150Glu missense_variant 5/8 ENSP00000497979.1 A0A3B3ITY5

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
30
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
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:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461590
Hom.:
0
Cov.:
31
AF XY:
0.00000138
AC XY:
1
AN XY:
727062
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
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:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152160
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
74318
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000329
Hom.:
0
Bravo
AF:
0.00000756

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 submitterclinical testingAmbry GeneticsApr 27, 2024The c.2438A>G (p.E813G) alteration is located in exon 24 (coding exon 23) of the WDR27 gene. This alteration results from a A to G substitution at nucleotide position 2438, causing the glutamic acid (E) at amino acid position 813 to be replaced by a glycine (G). 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
-0.089
T
BayesDel_noAF
Benign
-0.37
CADD
Benign
22
DANN
Uncertain
1.0
Eigen
Uncertain
0.20
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.61
D
LIST_S2
Benign
0.70
T;T
M_CAP
Benign
0.0093
T
MetaRNN
Benign
0.36
T;T
MetaSVM
Benign
-0.85
T
PrimateAI
Benign
0.40
T
PROVEAN
Pathogenic
-4.8
D;D
REVEL
Benign
0.26
Sift
Uncertain
0.010
D;D
Sift4G
Pathogenic
0.0010
D;D
Polyphen
0.98
.;D
Vest4
0.48
MVP
0.13
MPC
0.12
ClinPred
0.97
D
GERP RS
5.4
gMVP
0.33

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.

Other links and lift over

dbSNP: rs1271488866; hg19: chr6-169983017; API