7-151381679-A-C

Variant names:

• chr7-151381679-A-C
• NM_198285.3:c.1034T>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_198285.3(WDR86):​c.1034T>G​(p.Leu345Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 34)
  • Exomes 𝑓: 0.0000016 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR86 NM_198285.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.21
• Publications: 0 publications found

Genes affected

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR86	NM_198285.3	c.1034T>G	p.Leu345Arg	missense_variant	Exon 6 of 6	ENST00000334493.11	NP_938026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR86	ENST00000334493.11	c.1034T>G	p.Leu345Arg	missense_variant	Exon 6 of 6	5	NM_198285.3	ENSP00000335522.7

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000157 AC: 2 AN: 1277502 Hom.: 0 Cov.: 53 AF XY: 0.00000160 AC XY: 1 AN XY: 625614

African (AFR) AF: 0.00 AC: 0 AN: 24428

American (AMR) AF: 0.00 AC: 0 AN: 15070

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19268

East Asian (EAS) AF: 0.00 AC: 0 AN: 29050

South Asian (SAS) AF: 0.00 AC: 0 AN: 62224

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37650

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3714

European-Non Finnish (NFE) AF: 0.00000194 AC: 2 AN: 1033582

Other (OTH) AF: 0.00 AC: 0 AN: 52516

GnomAD4 genome Cov.: 34

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Dec 13, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1034T>G (p.L345R) alteration is located in exon 6 (coding exon 6) of the WDR86 gene. This alteration results from a T to G substitution at nucleotide position 1034, causing the leucine (L) at amino acid position 345 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	Benign	0.20
BayesDel_addAF	Benign	-0.0056	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.011	T;.
Eigen	Benign	0.11
Eigen_PC	Benign	0.055
FATHMM_MKL	Benign	0.58	D
LIST_S2	Benign	0.49	T;T
M_CAP	Pathogenic	0.76	D
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.93	T
PhyloP100		4.2
PrimateAI	Pathogenic	0.81	D
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.020	D;D
Polyphen		0.92	P;.
Vest4		0.18
MutPred		0.53		Gain of disorder (P = 0.0123);.;
MVP		0.42
MPC		1.4
ClinPred		0.97	D
GERP RS		4.5
Varity_R		0.61
Mutation Taster		=72/28	polymorphism

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

Other links and lift over

hg19: chr7-151078765;