NM_001083961.2:c.4170A>T

Variant names:

• chr19-36104534-A-T
• rs1008328
• NM_001083961.2:c.4170A>T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001083961.2(WDR62):​c.4170A>T​(p.Leu1390Phe) 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 nucleotide change resulting in the same amino acid substitution has been previously reported as Benign in Lovd.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.126

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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.05147147).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.4170A>T	p.Leu1390Phe	missense_variant	Exon 31 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.4170A>T	p.Leu1390Phe	missense_variant	Exon 31 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 6.84e-7 AC: 1 AN: 1461574 Hom.: 0 Cov.: 76 AF XY: 0.00000138 AC XY: 1 AN XY: 727104

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.055
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.78
CADD	Benign	5.9
DANN	Benign	0.45
DEOGEN2	Benign	0.00089	.;T
Eigen	Benign	-1.3
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.047	N
LIST_S2	Benign	0.083	T;T
M_CAP	Benign	0.0089	T
MetaRNN	Benign	0.051	T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	.;N
PrimateAI	Benign	0.37	T
PROVEAN	Benign	-0.38	N;N
REVEL	Benign	0.056
Sift	Benign	0.31	T;T
Sift4G	Benign	0.56	T;T
Polyphen		0.0020	B;B
Vest4		0.029
MutPred		0.36		.;Loss of phosphorylation at S1388 (P = 0.1262);
MVP		0.29
MPC		0.24
ClinPred		0.50	D
GERP RS		2.0
Varity_R		0.047
gMVP		0.045

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.090		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: rs1008328; hg19: chr19-36595436;