Genetic Variant WDR87:p.Val2908Ile (chr19-37884949-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_001291088.2(WDR87):c.8722G>A(p.Val2908Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000471 in 1,316,150 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000046 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000047 ( 0 hom. )

Consequence

WDR87
NM_001291088.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.983

Publications

1 publications found

Variant links:

Genes affected

WDR87 (HGNC:29934): (WD repeat domain 87)

WDR87 Gene-Disease associations (from GenCC):

cataract
Inheritance: AR Classification: LIMITED Submitted by: G2P

WDR87 links:

LOC105372395 (HGNC:):

LOC105372395 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.048734367).

BP6

Variant 19-37884949-C-T is Benign according to our data. Variant chr19-37884949-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3332987.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001291088.2. 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
	WDR87	NM_001291088.2	MANE Select	c.8722G>A	p.Val2908Ile	missense	Exon 6 of 6	NP_001278017.1	A0AA75ISB7
	WDR87	NM_031951.5		c.8605G>A	p.Val2869Ile	missense	Exon 6 of 6	NP_114157.4

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
WDR87	ENST00000447313.7	TSL:2 MANE Select	c.8722G>A	p.Val2908Ile	missense	Exon 6 of 6	ENSP00000405012.2	A0AA75ISB7
WDR87	ENST00000303868.5	TSL:2	c.8605G>A	p.Val2869Ile	missense	Exon 6 of 6	ENSP00000368025.3	Q6ZQQ6-1
ENSG00000291089	ENST00000801875.1		n.*108C>T		downstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000460

AC:

AN:

152076

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000735

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000413

AC:

AN:

48408

AF XY:

0.0000432

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000964

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000472

AC:

AN:

1164074

Hom.:

Cov.:

AF XY:

0.0000343

AC XY:

AN XY:

553844

show subpopulations

African (AFR)

AF:

0.0000408

AC:

AN:

24504

American (AMR)

AF:

0.00

AC:

AN:

12630

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

15638

East Asian (EAS)

AF:

0.00

AC:

AN:

29480

South Asian (SAS)

AF:

0.0000328

AC:

AN:

30500

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40640

Middle Eastern (MID)

AF:

0.000210

AC:

AN:

4766

European-Non Finnish (NFE)

AF:

0.0000532

AC:

AN:

958536

Other (OTH)

AF:

0.0000211

AC:

AN:

47380

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.470

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:

0.0000460

AC:

AN:

152076

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74284

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41408

American (AMR)

AF:

0.0000655

AC:

AN:

15258

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.000207

AC:

AN:

4824

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10588

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000735

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

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:

0.00

Hom.:

Bravo

AF:

0.0000227

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.00

AC:

ExAC

AF:

0.0000446

AC:

ClinVar

ClinVar submissions

Significance:Likely benign

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

0.097

BayesDel_addAF

Benign

-0.53

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.063

(source)

DANN

Benign

0.31

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0016

LIST_S2

Benign

0.28

M_CAP

Benign

0.0055

MetaRNN

Benign

0.049

MetaSVM

Benign

-0.94

PhyloP100

-0.98

PrimateAI

Benign

0.29

PROVEAN

Benign

-0.29

REVEL

Benign

0.0060

Sift

Benign

0.47

Sift4G

Benign

0.52

Polyphen

0.062

Vest4

0.030

MutPred

0.081

Gain of catalytic residue at P2910 (P = 0.0307)

MVP

0.014

ClinPred

0.012

GERP RS

-5.8

gMVP

0.032

Mutation Taster

=100/0

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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