Variant X-118393050-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_019045.5(WDR44):c.605A>C(p.Asp202Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000512 in 1,210,040 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 18 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000081 ( 0 hom., 3 hem., cov: 24)

Exomes 𝑓: 0.000048 ( 0 hom. 15 hem. )

Consequence

WDR44
NM_019045.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.17

Variant links:

Genes affected

WDR44 (HGNC:30512): (WD repeat domain 44) This gene encodes a protein that interacts with the small GTPase rab11. A similar protein in rat binds the GTP-containing active form of rab11. This protein may play a role in endosome recycling. Alternate splicing results in multiple transcript variants.[provided by RefSeq, May 2010]

WDR44 links:

WDR44 (HGNC:):

WDR44 links:

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ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.22238421).

BS2

High Hemizygotes in GnomAd4 at 3 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR44	NM_019045.5 linkuse as main transcript	c.605A>C	p.Asp202Ala	missense_variant	4/20	ENST00000254029.8	NP_061918.3	Q5JSH3-1
WDR44	NM_001184965.2 linkuse as main transcript	c.605A>C	p.Asp202Ala	missense_variant	4/20		NP_001171894.1	Q5JSH3-2
WDR44	NM_001184966.1 linkuse as main transcript	c.530A>C	p.Asp177Ala	missense_variant	3/18		NP_001171895.1	Q5JSH3-4
WDR44	XM_011531353.4 linkuse as main transcript	c.530A>C	p.Asp177Ala	missense_variant	3/19		XP_011529655.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR44	ENST00000254029.8 linkuse as main transcript	c.605A>C	p.Asp202Ala	missense_variant	4/20	1	NM_019045.5	ENSP00000254029.3		Q5JSH3-1

Frequencies

GnomAD3 genomes

AF:

0.0000805

AC:

AN:

111780

Hom.:

Cov.:

AF XY:

0.0000883

AC XY:

AN XY:

33960

show subpopulations

Gnomad AFR

AF:

0.0000651

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000327

AC:

AN:

183351

Hom.:

AF XY:

0.0000295

AC XY:

AN XY:

67831

show subpopulations

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 SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000733

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000483

AC:

AN:

1098260

Hom.:

Cov.:

AF XY:

0.0000413

AC XY:

AN XY:

363614

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:

0.0000629

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000805

AC:

AN:

111780

Hom.:

Cov.:

AF XY:

0.0000883

AC XY:

AN XY:

33960

show subpopulations

Gnomad4 AFR

AF:

0.0000651

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:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.000117

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.000164

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

Dec 02, 2022

The c.605A>C (p.D202A) alteration is located in exon 4 (coding exon 4) of the WDR44 gene. This alteration results from a A to C substitution at nucleotide position 605, causing the aspartic acid (D) at amino acid position 202 to be replaced by an alanine (A). 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

0.099

BayesDel_addAF

Benign

-0.090

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.12

.;T;.

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Benign

0.76

T;T;T

M_CAP

Pathogenic

0.47

MetaRNN

Benign

0.22

T;T;T

MetaSVM

Benign

-0.76

MutationAssessor

Benign

1.4

.;L;L

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.16

N;N;N

REVEL

Benign

0.28

Sift

Uncertain

0.011

D;D;D

Sift4G

Benign

0.72

T;T;T

Polyphen

0.21, 0.31

.;B;B

Vest4

0.41

MutPred

0.18

.;Gain of helix (P = 0.0349);Gain of helix (P = 0.0349);

MVP

0.58

MPC

0.29

ClinPred

0.28

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.19

gMVP

0.36

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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