Genetic Variant NM_001291088.2:c.8342G>A (chr19-37885329-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001291088.2(WDR87):c.8342G>A(p.Arg2781Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000264 in 1,551,388 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 Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

WDR87
NM_001291088.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.0610

Publications

3 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.

BP4

Computational evidence support a benign effect (MetaRNN=0.065494865).

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.8342G>A	p.Arg2781Gln	missense	Exon 6 of 6	NP_001278017.1	A0AA75ISB7
	WDR87	NM_031951.5		c.8225G>A	p.Arg2742Gln	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.8342G>A	p.Arg2781Gln	missense	Exon 6 of 6	ENSP00000405012.2	A0AA75ISB7
	WDR87	ENST00000303868.5	TSL:2	c.8225G>A	p.Arg2742Gln	missense	Exon 6 of 6	ENSP00000368025.3	Q6ZQQ6-1

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152146

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000102

AC:

AN:

156172

AF XY:

0.000109

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000918

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000496

Gnomad OTH exome

AF:

0.000456

GnomAD4 exome

AF:

0.0000272

AC:

AN:

1399242

Hom.:

Cov.:

AF XY:

0.0000232

AC XY:

AN XY:

690130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

31586

American (AMR)

AF:

0.000252

AC:

AN:

35686

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25168

East Asian (EAS)

AF:

0.0000560

AC:

AN:

35738

South Asian (SAS)

AF:

0.0000253

AC:

AN:

79186

European-Finnish (FIN)

AF:

0.0000203

AC:

AN:

49282

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5698

European-Non Finnish (NFE)

AF:

0.0000195

AC:

AN:

1078906

Other (OTH)

AF:

0.0000517

AC:

AN:

57992

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

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:

0.0000197

AC:

AN:

152146

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41424

American (AMR)

AF:

0.000131

AC:

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5188

South Asian (SAS)

AF:

0.00

AC:

AN:

4828

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

68024

Other (OTH)

AF:

0.00

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000108

Hom.:

Bravo

AF:

0.0000529

ExAC

AF:

0.0000790

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

0.11

BayesDel_addAF

Benign

-0.47

BayesDel_noAF

Benign

-0.60

CADD

Benign

(source)

DANN

Benign

0.80

Eigen

Benign

-0.71

Eigen_PC

Benign

-0.69

FATHMM_MKL

Benign

0.17

LIST_S2

Benign

0.56

M_CAP

Benign

0.023

MetaRNN

Benign

0.065

MetaSVM

Benign

-1.1

PhyloP100

0.061

PrimateAI

Benign

0.25

PROVEAN

Benign

-1.8

REVEL

Benign

0.021

Sift

Benign

0.039

Sift4G

Uncertain

0.019

Polyphen

0.37

Vest4

0.18

MVP

0.099

ClinPred

0.043

GERP RS

-0.79

gMVP

0.11

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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over