chr7-151381658-G-A

Position:

• chr7-151381658-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_198285.3(WDR86):​c.1055C>T​(p.Pro352Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000016 in 1,249,048 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/17 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P352R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.777

Genes affected

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

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.10711169).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR86	NM_198285.3	c.1055C>T	p.Pro352Leu	missense_variant	6/6	ENST00000334493.11

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR86	ENST00000334493.11	c.1055C>T	p.Pro352Leu	missense_variant	6/6	5	NM_198285.3	P1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 0.00000160 AC: 2 AN: 1249048 Hom.: 0 Cov.: 54 AF XY: 0.00000164 AC XY: 1 AN XY: 609840

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000703

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.: 34

Bravo AF: 0.00000378

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

May 26, 2024

The c.1055C>T (p.P352L) alteration is located in exon 6 (coding exon 6) of the WDR86 gene. This alteration results from a C to T substitution at nucleotide position 1055, causing the proline (P) at amino acid position 352 to be replaced by a leucine (L). 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	0.091
BayesDel_addAF	Benign	0.0012	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	14
DANN	Uncertain	0.99
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.032	N
LIST_S2	Benign	0.32	T;.
M_CAP	Pathogenic	0.36	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N;N
PROVEAN	Benign	-0.39	.;N
REVEL	Benign	0.037
Sift	Uncertain	0.0040	.;D
Sift4G	Benign	0.19	T;T
Vest4		0.048
MutPred		0.26		Loss of sheet (P = 7e-04);Loss of sheet (P = 7e-04);
MVP		0.17
ClinPred		0.55	D
GERP RS		-0.49

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

LitVar

Other links and lift over

dbSNP: rs1294105498; hg19: chr7-151078744;