Genetic Variant WDFY2:p.Ser75Cys (chr13-51675188-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_052950.4(WDFY2):c.224C>G(p.Ser75Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000539 in 1,613,908 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00022 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000037 ( 0 hom. )

Consequence

WDFY2
NM_052950.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.04

Publications

2 publications found

Variant links:

Genes affected

WDFY2 (HGNC:20482): (WD repeat and FYVE domain containing 2) This gene encodes a protein that contains two WD domains and an FYVE zinc finger region. The function of this gene is unknown. An alternatively spliced transcript variant of this gene may exist. [provided by RefSeq, Jul 2008]

WDFY2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.09084839).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_052950.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDFY2	NM_052950.4	MANE Select	c.224C>G	p.Ser75Cys	missense	Exon 3 of 12	NP_443182.1	Q96P53

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDFY2	ENST00000298125.7	TSL:1 MANE Select	c.224C>G	p.Ser75Cys	missense	Exon 3 of 12	ENSP00000298125.4	Q96P53
WDFY2	ENST00000923033.1		c.224C>G	p.Ser75Cys	missense	Exon 3 of 12	ENSP00000593092.1
WDFY2	ENST00000876143.1		c.224C>G	p.Ser75Cys	missense	Exon 3 of 12	ENSP00000546202.1

Frequencies

GnomAD3 genomes

AF:

0.000217

AC:

AN:

152144

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000748

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

GnomAD2 exomes

AF:

0.0000438

AC:

AN:

251258

AF XY:

0.0000295

show subpopulations

Gnomad AFR exome

AF:

0.000369

Gnomad AMR exome

AF:

0.0000868

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

0.0000369

AC:

AN:

1461646

Hom.:

Cov.:

AF XY:

0.0000399

AC XY:

AN XY:

727126

show subpopulations

African (AFR)

AF:

0.000867

AC:

AN:

33464

American (AMR)

AF:

0.0000895

AC:

AN:

44714

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26126

East Asian (EAS)

AF:

0.00

AC:

AN:

39684

South Asian (SAS)

AF:

0.0000464

AC:

AN:

86248

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53394

Middle Eastern (MID)

AF:

0.000173

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00000180

AC:

AN:

1111864

Other (OTH)

AF:

0.000232

AC:

AN:

60386

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.450

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000217

AC:

AN:

152262

Hom.:

Cov.:

AF XY:

0.000188

AC XY:

AN XY:

74454

show subpopulations

African (AFR)

AF:

0.000746

AC:

AN:

41554

American (AMR)

AF:

0.000131

AC:

AN:

15294

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5184

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10604

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68018

Other (OTH)

AF:

0.00

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000504

Hom.:

Bravo

AF:

0.000321

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.26

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Benign

0.0096

Eigen

Benign

-0.092

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.89

LIST_S2

Benign

0.82

M_CAP

Benign

0.010

MetaRNN

Benign

0.091

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.21

PhyloP100

2.0

PrimateAI

Uncertain

0.72

PROVEAN

Benign

-0.59

REVEL

Benign

0.13

Sift

Benign

0.19

Sift4G

Benign

0.22

Polyphen

0.0020

Vest4

0.45

MVP

0.70

MPC

0.35

ClinPred

0.022

GERP RS

6.1

Varity_R

0.074

gMVP

0.43

Mutation Taster

=76/24

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over