7-151395889-C-A

Position:

• chr7-151395889-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_198285.3(WDR86):​c.613G>T​(p.Gly205Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.169

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.801

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR86	NM_198285.3	c.613G>T	p.Gly205Cys	missense_variant	3/6	ENST00000334493.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR86	ENST00000334493.11	c.613G>T	p.Gly205Cys	missense_variant	3/6	5	NM_198285.3	P1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000431 AC: 1 AN: 232122 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 126328

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 SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000952

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1449932 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 720652

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 02, 2022

The c.613G>T (p.G205C) alteration is located in exon 3 (coding exon 3) of the WDR86 gene. This alteration results from a G to T substitution at nucleotide position 613, causing the glycine (G) at amino acid position 205 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	0.10
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	3.7
DANN	Uncertain	0.99
DEOGEN2	Benign	0.079	T;.;.;.;.
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.64	T;T;T;.;T
M_CAP	Uncertain	0.22	D
MetaRNN	Pathogenic	0.80	D;D;D;D;D
MetaSVM	Uncertain	-0.076	T
MutationAssessor	Benign	1.9	L;.;.;.;L
MutationTaster	Benign	1.0	N;N;N
PrimateAI	Benign	0.41	T
PROVEAN	Pathogenic	-7.0	D;.;.;D;D
REVEL	Benign	0.16
Sift	Uncertain	0.0050	D;.;.;D;D
Sift4G	Uncertain	0.0020	D;D;D;D;D
Polyphen		0.99	D;.;.;.;.
Vest4		0.26
MutPred		0.76		Gain of catalytic residue at P204 (P = 0.0086);.;.;.;Gain of catalytic residue at P204 (P = 0.0086);
MVP		0.47
MPC		0.39
ClinPred		0.18	T
GERP RS		-7.1
Varity_R		0.41
gMVP		0.47

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs139197034; hg19: chr7-151092975;