19-36103640-C-G

Variant summary

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

The NM_001083961.2(WDR62):c.3812C>G(p.Ala1271Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign 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. A1271V) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.401

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.07715994).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
WDR62	NM_001083961.2	c.3812C>G	p.Ala1271Gly	missense_variant	30/32	ENST00000401500.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
WDR62	ENST00000401500.7	c.3812C>G	p.Ala1271Gly	missense_variant	30/32	1	NM_001083961.2	P4

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.35	T
BayesDel_noAF	Benign	-0.74
Cadd	Benign	1.5
Dann	Benign	0.49
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.041	N
LIST_S2	Benign	0.66	T;T
M_CAP	Benign	0.027	D
MetaRNN	Benign	0.077	T;T
MetaSVM	Benign	-1.0	T
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.24	T
PROVEAN	Benign	-1.9	N;N
REVEL	Benign	0.044
Sift	Benign	0.061	T;T
Sift4G	Benign	0.16	T;T
Polyphen		0.29	B;B
Vest4		0.056
MutPred		0.14		.;Gain of loop (P = 0.0851);
MVP		0.43
MPC		0.24
ClinPred		0.10	T
GERP RS		-2.7
Varity_R		0.090
gMVP		0.071

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: rs111294536; hg19: chr19-36594542;