rs146180912

Positions:

• chr19-36073523-A-C
• chr19-36073523-A-G

Variant summary

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

The ENST00000401500.7(WDR62):​c.1225A>C​(p.Asn409His) 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. N409D) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: WDR62 ENST00000401500.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.56

Genes affected

WDR62 (HGNC:24502): (WD repeat domain 62) This gene is proposed to play a role in cerebral cortical development. Mutations in this gene have been associated with microencephaly, cortical malformations, and cognitive disability. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2011]

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, 0.759

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.1225A>C	p.Asn409His	missense_variant	9/32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.1225A>C	p.Asn409His	missense_variant	9/32	1	NM_001083961.2	ENSP00000384792	P4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Benign	-0.071	T
BayesDel_noAF	Benign	-0.34
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.085	.;T
Eigen	Uncertain	0.59
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.027	D
MetaRNN	Pathogenic	0.76	D;D
MetaSVM	Benign	-0.49	T
MutationAssessor	Benign	1.5	L;L
MutationTaster	Benign	1.0	D;D;D;D
PrimateAI	Uncertain	0.58	T
PROVEAN	Uncertain	-2.7	D;D
REVEL	Benign	0.23
Sift	Uncertain	0.025	D;D
Sift4G	Uncertain	0.040	D;D
Polyphen		1.0	D;D
Vest4		0.58
MutPred		0.66		Loss of catalytic residue at N409 (P = 0.0571);Loss of catalytic residue at N409 (P = 0.0571);
MVP		0.77
MPC		0.80
ClinPred		0.98	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.30
gMVP		0.58

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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: chr19-36564425;