Variant chr2-28912609-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_015131.3(WDR43):c.505A>G(p.Ser169Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000874 in 1,613,934 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 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. S169N) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.00013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000083 ( 0 hom. )

Consequence

WDR43
NM_015131.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.36

Variant links:

Genes affected

WDR43 (HGNC:28945): (WD repeat domain 43) Enables RNA binding activity. Involved in positive regulation of rRNA processing and positive regulation of transcription by RNA polymerase I. Located in fibrillar center. [provided by Alliance of Genome Resources, Apr 2022]

WDR43 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.026393265).

BS2

High AC in GnomAd4 at 20 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR43	NM_015131.3 linkuse as main transcript	c.505A>G	p.Ser169Gly	missense_variant	4/18	ENST00000407426.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris
WDR43	ENST00000407426.8 linkuse as main transcript	c.505A>G	p.Ser169Gly	missense_variant	4/18	1	NM_015131.3	P1
WDR43	ENST00000440983.1 linkuse as main transcript	c.238A>G	p.Ser80Gly	missense_variant	4/5	4
WDR43	ENST00000296126.6 linkuse as main transcript	c.-39A>G		5_prime_UTR_variant	3/8	5

Frequencies

GnomAD3 genomes

AF:

0.000131

AC:

AN:

152196

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000654

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:

0.000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000144

AC:

AN:

249146

Hom.:

AF XY:

0.000163

AC XY:

AN XY:

135174

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000783

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:

0.0000531

Gnomad OTH exome

AF:

0.000496

GnomAD4 exome

AF:

0.0000828

AC:

121

AN:

1461620

Hom.:

Cov.:

AF XY:

0.0000798

AC XY:

AN XY:

727094

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000760

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:

0.0000693

Gnomad4 OTH exome

AF:

0.000166

GnomAD4 genome

AF:

0.000131

AC:

AN:

152314

Hom.:

Cov.:

AF XY:

0.000134

AC XY:

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000147

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000282

Hom.:

Bravo

AF:

0.000193

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000910

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.0000593

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

May 14, 2024

The c.505A>G (p.S169G) alteration is located in exon 4 (coding exon 4) of the WDR43 gene. This alteration results from a A to G substitution at nucleotide position 505, causing the serine (S) at amino acid position 169 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

AlphaMissense

Benign

0.074

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.38

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.032

T;.

Eigen

Benign

-0.13

Eigen_PC

Benign

0.12

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.79

T;T

M_CAP

Benign

0.028

MetaRNN

Benign

0.026

T;T

MetaSVM

Benign

-0.67

MutationAssessor

Benign

-0.21

N;.

MutationTaster

Benign

0.97

PrimateAI

Uncertain

0.49

PROVEAN

Benign

-0.83

N;N

REVEL

Benign

0.086

Sift

Benign

0.32

T;T

Sift4G

Benign

0.26

T;T

Polyphen

0.038

B;.

Vest4

0.13

MutPred

0.46

Loss of stability (P = 0.0639);.;

MVP

0.24

MPC

0.16

ClinPred

0.079

GERP RS

5.8

Varity_R

0.12

gMVP

0.25

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