Genetic Variant NM_198285.3:c.805C>T (chr7-151385145-G-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_198285.3(WDR86):c.805C>T(p.Arg269Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,460,418 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

WDR86
NM_198285.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.78

Publications

3 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: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19437867).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3 link	c.805C>T	p.Arg269Cys	missense_variant	Exon 4 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.805C>T	p.Arg269Cys	missense_variant	Exon 4 of 6	5	NM_198285.3	ENSP00000335522.7		Q86TI4-3

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000404

AC:

AN:

247828

AF XY:

0.00

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:

0.00000890

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000411

AC:

AN:

1460418

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

726522

show subpopulations

African (AFR)

AF:

0.0000299

AC:

AN:

33464

American (AMR)

AF:

0.00

AC:

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26116

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86198

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52672

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5422

European-Non Finnish (NFE)

AF:

0.00000270

AC:

AN:

1111822

Other (OTH)

AF:

0.0000166

AC:

AN:

60316

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.492

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.000111

Hom.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 24, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.805C>T (p.R269C) alteration is located in exon 4 (coding exon 4) of the WDR86 gene. This alteration results from a C to T substitution at nucleotide position 805, causing the arginine (R) at amino acid position 269 to be replaced by a cysteine (C). 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

0.11

BayesDel_addAF

Uncertain

0.048

BayesDel_noAF

Benign

-0.43

CADD

Benign

(source)

DANN

Uncertain

0.99

Eigen

Benign

-0.18

Eigen_PC

Benign

-0.16

FATHMM_MKL

Benign

0.75

LIST_S2

Benign

0.40

M_CAP

Benign

0.027

MetaRNN

Benign

0.19

MetaSVM

Benign

-1.0

PhyloP100

2.8

PROVEAN

Benign

-0.89

REVEL

Benign

0.11

Sift

Uncertain

0.0070

Sift4G

Uncertain

0.059

Vest4

0.33

MutPred

0.42

Gain of sheet (P = 0.0061);

MVP

0.47

ClinPred

0.48

GERP RS

3.1

Varity_R

0.15

gMVP

0.20

Mutation Taster

=88/12

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

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NM_198285.3:c.805C>T

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over