Genetic Variant WDR86:p.Gly325Ser (chr7-151381740-C-T) – 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_198285.3(WDR86):c.973G>A(p.Gly325Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000456 in 1,514,292 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 0.00017 ( 0 hom., cov: 34)

Exomes 𝑓: 0.000032 ( 0 hom. )

Consequence

WDR86
NM_198285.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.31

Publications

1 publications found

Variant links:

Genes affected

WDR86 (HGNC:28020): (WD repeat domain 86)

WDR86 links:

Genome browser will be placed here

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=0.07209143).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3 link	c.973G>A	p.Gly325Ser	missense_variant	Exon 6 of 6	ENST00000334493.11	NP_938026.2	Q86TI4-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR86	ENST00000334493.11 link	c.973G>A	p.Gly325Ser	missense_variant	Exon 6 of 6	5	NM_198285.3	ENSP00000335522.7		Q86TI4-3

Frequencies

GnomAD3 genomes

AF:

0.000171

AC:

AN:

152078

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000604

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.000478

GnomAD2 exomes

AF:

0.0000839

AC:

AN:

107300

AF XY:

0.000121

show subpopulations

Gnomad AFR exome

AF:

0.00147

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000316

AC:

AN:

1362098

Hom.:

Cov.:

AF XY:

0.0000284

AC XY:

AN XY:

669978

show subpopulations

African (AFR)

AF:

0.000710

AC:

AN:

29584

American (AMR)

AF:

0.00

AC:

AN:

29770

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22574

East Asian (EAS)

AF:

0.00

AC:

AN:

34946

South Asian (SAS)

AF:

0.00

AC:

AN:

74092

European-Finnish (FIN)

AF:

0.00

AC:

AN:

45656

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4854

European-Non Finnish (NFE)

AF:

0.0000207

AC:

AN:

1064442

Other (OTH)

AF:

0.00

AC:

AN:

56180

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000171

AC:

AN:

152194

Hom.:

Cov.:

AF XY:

0.000121

AC XY:

AN XY:

74400

show subpopulations

African (AFR)

AF:

0.000602

AC:

AN:

41532

American (AMR)

AF:

0.00

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5152

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67976

Other (OTH)

AF:

0.000473

AC:

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.000185

ESP6500AA

AF:

0.000704

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000570

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3474

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 27, 2022

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.973G>A (p.G325S) alteration is located in exon 6 (coding exon 6) of the WDR86 gene. This alteration results from a G to A substitution at nucleotide position 973, causing the glycine (G) at amino acid position 325 to be replaced by a serine (S). 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

Benign

0.12

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.37

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.050

T;.

Eigen

Benign

-0.25

Eigen_PC

Benign

-0.11

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.77

T;T

M_CAP

Pathogenic

0.77

MetaRNN

Benign

0.072

T;T

MetaSVM

Benign

-1.0

PhyloP100

2.3

PrimateAI

Uncertain

0.62

PROVEAN

Uncertain

-3.3

D;.

REVEL

Benign

0.12

Sift

Benign

0.21

T;.

Sift4G

Uncertain

0.038

D;T

Polyphen

0.63

P;.

Vest4

0.078

MVP

0.32

MPC

0.53

ClinPred

0.13

GERP RS

3.5

Varity_R

0.20

Mutation Taster

=86/14

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.050

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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chr7-151381740-C-T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over