chr7-151409484-C-T

Position:

• chr7-151409484-C-T

Variant summary

Our verdict is Likely pathogenic. Variant got 6 ACMG points: 6P and 0B. PM2 PP3_Strong

The NM_198285.3(WDR86):​c.106G>A​(p.Asp36Asn) 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: 5.32

Genes affected

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

WDR86-AS1 (HGNC:41186): (WDR86 antisense RNA 1)

ACMG classification

Verdict is Likely_pathogenic. Variant got 6 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.944

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR86	NM_198285.3	c.106G>A	p.Asp36Asn	missense_variant	1/6	ENST00000334493.11
WDR86-AS1	NR_109857.1	n.222+102C>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR86	ENST00000334493.11	c.106G>A	p.Asp36Asn	missense_variant	1/6	5	NM_198285.3	P1
WDR86-AS1	ENST00000489632.5	n.222+102C>T		intron_variant, non_coding_transcript_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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

Mar 25, 2024

The c.106G>A (p.D36N) alteration is located in exon 1 (coding exon 1) of the WDR86 gene. This alteration results from a G to A substitution at nucleotide position 106, causing the aspartic acid (D) at amino acid position 36 to be replaced by an asparagine (N). 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	Pathogenic	0.94
BayesDel_addAF	Uncertain	0.12	D
BayesDel_noAF	Uncertain	-0.070
CADD	Pathogenic	32
DANN	Uncertain	1.0
DEOGEN2	Benign	0.050	T;.
Eigen	Pathogenic	0.73
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Uncertain	0.94	D;D
M_CAP	Pathogenic	0.60	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Pathogenic	0.98	D
MutationAssessor	Pathogenic	3.4	M;M
MutationTaster	Benign	0.94	D;D;D
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.7	D;D
REVEL	Pathogenic	0.82
Sift	Pathogenic	0.0	D;D
Sift4G	Uncertain	0.0050	D;D
Polyphen		1.0	D;.
Vest4		0.65
MutPred		0.84		Loss of phosphorylation at T38 (P = 0.1229);Loss of phosphorylation at T38 (P = 0.1229);
MVP		0.73
MPC		1.1
ClinPred		0.99	D
GERP RS		3.9
Varity_R		0.67
gMVP		0.75

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr7-151106570;