NM_001083961.2:c.1043+439C>T

Variant names:

• chr19-36072155-C-T
• rs2023865
• NM_001083961.2:c.1043+439C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001083961.2(WDR62):​c.1043+439C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.285 in 152,104 control chromosomes in the GnomAD database, including 6,429 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.28 (6429 hom., cov: 33)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.227
• Publications: 6 publications found

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]

WDR62 Gene-Disease associations (from GenCC):

• microcephaly 2, primary, autosomal recessive, with or without cortical malformations

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, Ambry Genetics, Illumina, G2P, ClinGen
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001083961.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	NM_001083961.2	MANE Select	c.1043+439C>T		intron	N/A	NP_001077430.1
	WDR62	NM_001411145.1		c.1043+439C>T		intron	N/A	NP_001398074.1
	WDR62	NM_173636.5		c.1043+439C>T		intron	N/A	NP_775907.4

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	ENST00000401500.7	TSL:1 MANE Select	c.1043+439C>T		intron	N/A	ENSP00000384792.1
	WDR62	ENST00000587391.6	TSL:1	n.1043+439C>T		intron	N/A	ENSP00000465525.1
	WDR62	ENST00000679714.1		c.1043+439C>T		intron	N/A	ENSP00000506627.1

Frequencies

GnomAD3 genomes AF: 0.285 AC: 43269 AN: 151988 Hom.: 6431 Cov.: 33

Gnomad AFR AF: 0.227

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.326

Gnomad OTH AF: 0.285

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.285 AC: 43285 AN: 152104 Hom.: 6429 Cov.: 33 AF XY: 0.283 AC XY: 21028 AN XY: 74344

African (AFR) AF: 0.227 AC: 9403 AN: 41466

American (AMR) AF: 0.268 AC: 4094 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1373 AN: 5168

South Asian (SAS) AF: 0.180 AC: 869 AN: 4826

European-Finnish (FIN) AF: 0.340 AC: 3594 AN: 10562

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.326 AC: 22136 AN: 68006

Other (OTH) AF: 0.285 AC: 603 AN: 2116

Alfa AF: 0.303 Hom.: 4595

Bravo AF: 0.275

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	3.1
DANN	Benign	0.67
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2023865; hg19: chr19-36563057;