Variant 2-223878693-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 ENST00000233055.9(WDFY1):c.1211C>T(p.Ala404Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00027 in 1,614,064 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 (★).

Frequency

Genomes: 𝑓 0.00027 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00027 ( 0 hom. )

Consequence

WDFY1
ENST00000233055.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.31

Variant links:

Genes affected

WDFY1 (HGNC:20451): (WD repeat and FYVE domain containing 1) The protein encoded by this gene is a phosphatidylinositol 3-phosphate binding protein, which contains a FYVE zinc finger domain and multiple WD-40 repeat domains. When exogenously expressed, it localizes to early endosomes. Mutagenesis analysis demonstrates that this endosomal localization is mediated by the FYVE domain. [provided by RefSeq, Jan 2015]

WDFY1 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=0.41750968).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDFY1	NM_020830.5 linkuse as main transcript	c.1211C>T	p.Ala404Val	missense_variant	12/12	ENST00000233055.9	NP_065881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDFY1	ENST00000233055.9 linkuse as main transcript	c.1211C>T	p.Ala404Val	missense_variant	12/12	1	NM_020830.5	ENSP00000233055	P1
WDFY1	ENST00000462702.1 linkuse as main transcript			upstream_gene_variant		3

Frequencies

GnomAD3 genomes

AF:

0.000269

AC:

AN:

152170

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000544

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000241

AC:

AN:

249090

Hom.:

AF XY:

0.000245

AC XY:

AN XY:

134816

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000462

Gnomad NFE exome

AF:

0.000493

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.000270

AC:

394

AN:

1461776

Hom.:

Cov.:

AF XY:

0.000267

AC XY:

194

AN XY:

727190

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

Gnomad4 AMR exome

AF:

0.0000894

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000374

Gnomad4 NFE exome

AF:

0.000340

Gnomad4 OTH exome

AF:

0.000149

GnomAD4 genome

AF:

0.000269

AC:

AN:

152288

Hom.:

Cov.:

AF XY:

0.000201

AC XY:

AN XY:

74460

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.000544

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000422

Hom.:

Bravo

AF:

0.000208

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000465

AC:

ExAC

AF:

0.000288

AC:

EpiCase

AF:

0.000654

EpiControl

AF:

0.000830

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

Oct 26, 2022

The c.1211C>T (p.A404V) alteration is located in exon 12 (coding exon 12) of the WDFY1 gene. This alteration results from a C to T substitution at nucleotide position 1211, causing the alanine (A) at amino acid position 404 to be replaced by a valine (V). 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

Uncertain

0.44

BayesDel_addAF

Benign

-0.16

BayesDel_noAF

Uncertain

-0.050

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.027

Eigen

Uncertain

0.58

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

1.0

LIST_S2

Uncertain

0.94

M_CAP

Benign

0.029

MetaRNN

Benign

0.42

MetaSVM

Benign

-0.55

MutationAssessor

Benign

1.9

MutationTaster

Benign

1.0

PrimateAI

Uncertain

0.73

PROVEAN

Benign

-0.67

REVEL

Benign

0.25

Sift

Benign

0.047

Sift4G

Benign

0.10

Polyphen

1.0

Vest4

0.64

MVP

0.69

MPC

0.57

ClinPred

0.14

GERP RS

5.5

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.13

gMVP

0.45

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