19-36095907-C-G

Variant names:

• chr19-36095907-C-G
• rs1548506
• NM_001083961.2:c.2468-1120C>G

Variant summary

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

The NM_001083961.2(WDR62):​c.2468-1120C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.605 in 152,120 control chromosomes in the GnomAD database, including 28,189 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 0.61 (28189 hom., cov: 32)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.352
• Publications: 5 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=-1.01).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.682 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
WDR62	NM_001083961.2	c.2468-1120C>G		intron_variant	Intron 20 of 31	ENST00000401500.7	NP_001077430.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
WDR62	ENST00000401500.7	c.2468-1120C>G		intron_variant	Intron 20 of 31	1	NM_001083961.2	ENSP00000384792.1

Frequencies

GnomAD3 genomes AF: 0.605 AC: 91969 AN: 152002 Hom.: 28162 Cov.: 32

Gnomad AFR AF: 0.689

Gnomad AMI AF: 0.387

Gnomad AMR AF: 0.628

Gnomad ASJ AF: 0.526

Gnomad EAS AF: 0.564

Gnomad SAS AF: 0.414

Gnomad FIN AF: 0.621

Gnomad MID AF: 0.598

Gnomad NFE AF: 0.570

Gnomad OTH AF: 0.605

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

GnomAD4 genome AF: 0.605 AC: 92042 AN: 152120 Hom.: 28189 Cov.: 32 AF XY: 0.605 AC XY: 45002 AN XY: 74386

African (AFR) AF: 0.689 AC: 28560 AN: 41474

American (AMR) AF: 0.629 AC: 9621 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.526 AC: 1825 AN: 3470

East Asian (EAS) AF: 0.563 AC: 2907 AN: 5160

South Asian (SAS) AF: 0.413 AC: 1992 AN: 4820

European-Finnish (FIN) AF: 0.621 AC: 6585 AN: 10596

Middle Eastern (MID) AF: 0.592 AC: 174 AN: 294

European-Non Finnish (NFE) AF: 0.570 AC: 38753 AN: 67980

Other (OTH) AF: 0.602 AC: 1273 AN: 2114

Alfa AF: 0.480 Hom.: 1404

Bravo AF: 0.614

Asia WGS AF: 0.460 AC: 1599 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	2.4
DANN	Benign	0.65
PhyloP100		-0.35
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: rs1548506; hg19: chr19-36586809;