chr7-151381931-C-T

Position:

• chr7-151381931-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_198285.3(WDR86):​c.913G>A​(p.Gly305Arg) variant causes a missense change. 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: 32)
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.18

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.849

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR86	NM_198285.3	c.913G>A	p.Gly305Arg	missense_variant	5/6	ENST00000334493.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR86	ENST00000334493.11	c.913G>A	p.Gly305Arg	missense_variant	5/6	5	NM_198285.3	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

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

Jan 30, 2024

The c.913G>A (p.G305R) alteration is located in exon 5 (coding exon 5) of the WDR86 gene. This alteration results from a G to A substitution at nucleotide position 913, causing the glycine (G) at amino acid position 305 to be replaced by an arginine (R). 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	Uncertain	0.56
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.082	T;.
Eigen	Benign	0.061
Eigen_PC	Benign	-0.022
FATHMM_MKL	Benign	0.57	D
LIST_S2	Benign	0.74	T;T
MetaRNN	Pathogenic	0.85	D;D
MetaSVM	Uncertain	-0.14	T
MutationTaster	Benign	1.0	D;D;N
PrimateAI	Uncertain	0.76	T
PROVEAN	Pathogenic	-6.9	D;.
REVEL	Uncertain	0.30
Sift	Pathogenic	0.0	D;.
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.59
MutPred		0.69		Gain of MoRF binding (P = 0.0039);.;
MVP		0.46
MPC		1.3
ClinPred		0.99	D
GERP RS		3.6
Varity_R		0.55

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-151079017;