NM_001083961.2:c.2057C>T

Variant names:

• chr19-36091222-C-T
• rs797046107
• NM_001083961.2:c.2057C>T

Variant summary

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

The NM_001083961.2(WDR62):​c.2057C>T​(p.Thr686Ile) 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. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 33)
• Consequence: WDR62 NM_001083961.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.393

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=0.22859535).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.2057C>T	p.Thr686Ile	missense_variant	Exon 17 of 32	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.2057C>T	p.Thr686Ile	missense_variant	Exon 17 of 32	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 33

GnomAD4 genome Cov.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2015

Genetic Services Laboratory, University of Chicago

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.49
BayesDel_addAF	Benign	-0.095	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Benign	0.95
DEOGEN2	Benign	0.031	.;T
Eigen	Benign	0.12
Eigen_PC	Benign	0.14
FATHMM_MKL	Benign	0.18	N
LIST_S2	Uncertain	0.95	D;D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.23	T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.26	N;N
PrimateAI	Uncertain	0.66	T
PROVEAN	Benign	0.44	N;N
REVEL	Benign	0.15
Sift	Benign	0.53	T;T
Sift4G	Benign	1.0	T;T
Polyphen		1.0	D;D
Vest4		0.40
MutPred		0.42		Loss of disorder (P = 0.0813);Loss of disorder (P = 0.0813);
MVP		0.70
MPC		0.77
ClinPred		0.68	D
GERP RS		5.3
Varity_R		0.082
gMVP		0.24

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: rs797046107; hg19: chr19-36582124;