Genetic Variant WDR87:p.Arg2776Gln (chr19-37885344-C-T) – ACMG Classification: Benign (-16 pts)

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001291088.2(WDR87):c.8327G>A(p.Arg2776Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0072 in 1,551,678 control chromosomes in the GnomAD database, including 62 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R2776W) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0039 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0076 ( 61 hom. )

Consequence

WDR87
NM_001291088.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.979

Publications

8 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006880492).

BP6

Variant 19-37885344-C-T is Benign according to our data. Variant chr19-37885344-C-T is described in ClinVar as Benign. ClinVar VariationId is 1287795.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAdExome4 at 61 AR gene

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.8327G>A	p.Arg2776Gln	missense	Exon 6 of 6	NP_001278017.1	A0AA75ISB7
	WDR87	NM_031951.5		c.8210G>A	p.Arg2737Gln	missense	Exon 6 of 6	NP_114157.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR87	ENST00000447313.7	TSL:2 MANE Select	c.8327G>A	p.Arg2776Gln	missense	Exon 6 of 6	ENSP00000405012.2	A0AA75ISB7
	WDR87	ENST00000303868.5	TSL:2	c.8210G>A	p.Arg2737Gln	missense	Exon 6 of 6	ENSP00000368025.3	Q6ZQQ6-1

Frequencies

GnomAD3 genomes

AF:

0.00390

AC:

594

AN:

152130

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00152

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000720

Gnomad ASJ

AF:

0.00173

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000471

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00741

Gnomad OTH

AF:

0.00239

GnomAD2 exomes

AF:

0.00355

AC:

556

AN:

156620

AF XY:

0.00338

show subpopulations

Gnomad AFR exome

AF:

0.00152

Gnomad AMR exome

AF:

0.000851

Gnomad ASJ exome

AF:

0.00200

Gnomad EAS exome

AF:

0.0000918

Gnomad FIN exome

AF:

0.00119

Gnomad NFE exome

AF:

0.00770

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00756

AC:

10580

AN:

1399430

Hom.:

Cov.:

AF XY:

0.00731

AC XY:

5043

AN XY:

690218

show subpopulations

African (AFR)

AF:

0.00139

AC:

AN:

31598

American (AMR)

AF:

0.000728

AC:

AN:

35702

Ashkenazi Jewish (ASJ)

AF:

0.00203

AC:

AN:

25178

East Asian (EAS)

AF:

0.0000839

AC:

AN:

35738

South Asian (SAS)

AF:

0.000151

AC:

AN:

79226

European-Finnish (FIN)

AF:

0.00126

AC:

AN:

49298

Middle Eastern (MID)

AF:

0.000176

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.00936

AC:

10104

AN:

1078974

Other (OTH)

AF:

0.00477

AC:

277

AN:

58018

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

696

1392

2087

2783

3479

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

412

824

1236

1648

2060

<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:

0.00390

AC:

594

AN:

152248

Hom.:

Cov.:

AF XY:

0.00361

AC XY:

269

AN XY:

74430

show subpopulations

African (AFR)

AF:

0.00152

AC:

AN:

41550

American (AMR)

AF:

0.000720

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00173

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.000471

AC:

AN:

10606

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00741

AC:

504

AN:

68018

Other (OTH)

AF:

0.00237

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

106

141

176

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:

0.00584

Hom.:

Bravo

AF:

0.00406

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.0138

AC:

ESP6500AA

AF:

0.00289

AC:

ESP6500EA

AF:

0.00817

AC:

ExAC

AF:

0.00262

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (3)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.10

BayesDel_addAF

Benign

-0.50

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

Eigen

Uncertain

0.25

Eigen_PC

Benign

0.22

FATHMM_MKL

Benign

0.60

LIST_S2

Benign

0.61

M_CAP

Benign

0.044

MetaRNN

Benign

0.0069

MetaSVM

Benign

-1.1

PhyloP100

0.98

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.7

REVEL

Benign

0.086

Sift

Benign

0.077

Sift4G

Benign

0.066

Polyphen

1.0

Vest4

0.26

MVP

0.25

ClinPred

0.038

GERP RS

2.6

gMVP

0.15

Mutation Taster

=96/4

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.14

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