chr19-36058782-G-A

Variant names:

• chr19-36058782-G-A
• rs61742664
• NM_001083961.2:c.180G>A

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001083961.2(WDR62):​c.180G>A​(p.Val60Val) variant causes a splice region, synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0519 in 1,613,680 control chromosomes in the GnomAD database, including 4,355 homozygotes. In-silico tool predicts a benign outcome for this variant. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.050 (405 hom., cov: 33)
  • Exomes 𝑓: 0.052 (3950 hom.)
• Consequence: WDR62 NM_001083961.2 splice_region, synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 1.38
• Publications: 13 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.6).
• BP6: Variant 19-36058782-G-A is Benign according to our data. Variant chr19-36058782-G-A is described in ClinVar as Benign. ClinVar VariationId is 160258.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.38 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.211 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	NM_001083961.2	MANE Select	c.180G>A	p.Val60Val	splice_region synonymous	Exon 2 of 32	NP_001077430.1
	WDR62	NM_001411145.1		c.180G>A	p.Val60Val	splice_region synonymous	Exon 2 of 32	NP_001398074.1
	WDR62	NM_173636.5		c.180G>A	p.Val60Val	splice_region synonymous	Exon 2 of 32	NP_775907.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	ENST00000401500.7	TSL:1 MANE Select	c.180G>A	p.Val60Val	splice_region synonymous	Exon 2 of 32	ENSP00000384792.1
	WDR62	ENST00000587391.6	TSL:1	n.180G>A		splice_region non_coding_transcript_exon	Exon 2 of 30	ENSP00000465525.1
	WDR62	ENST00000679714.1		c.180G>A	p.Val60Val	splice_region synonymous	Exon 2 of 32	ENSP00000506627.1

Frequencies

GnomAD3 genomes AF: 0.0497 AC: 7558 AN: 152200 Hom.: 403 Cov.: 33

Gnomad AFR AF: 0.0242

Gnomad AMI AF: 0.00877

Gnomad AMR AF: 0.0787

Gnomad ASJ AF: 0.0680

Gnomad EAS AF: 0.221

Gnomad SAS AF: 0.203

Gnomad FIN AF: 0.0328

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.0367

Gnomad OTH AF: 0.0568

GnomAD2 exomes AF: 0.0805 AC: 20196 AN: 250918 AF XY: 0.0838

Gnomad AFR exome AF: 0.0251

Gnomad AMR exome AF: 0.100

Gnomad ASJ exome AF: 0.0674

Gnomad EAS exome AF: 0.221

Gnomad FIN exome AF: 0.0360

Gnomad NFE exome AF: 0.0380

Gnomad OTH exome AF: 0.0664

GnomAD4 exome AF: 0.0522 AC: 76238 AN: 1461362 Hom.: 3950 Cov.: 31 AF XY: 0.0562 AC XY: 40832 AN XY: 727020

African (AFR) AF: 0.0228 AC: 762 AN: 33472

American (AMR) AF: 0.0977 AC: 4369 AN: 44700

Ashkenazi Jewish (ASJ) AF: 0.0710 AC: 1856 AN: 26134

East Asian (EAS) AF: 0.209 AC: 8291 AN: 39682

South Asian (SAS) AF: 0.191 AC: 16439 AN: 86206

European-Finnish (FIN) AF: 0.0358 AC: 1913 AN: 53366

Middle Eastern (MID) AF: 0.0524 AC: 301 AN: 5748

European-Non Finnish (NFE) AF: 0.0345 AC: 38336 AN: 1111682

Other (OTH) AF: 0.0658 AC: 3971 AN: 60372

GnomAD4 genome AF: 0.0497 AC: 7570 AN: 152318 Hom.: 405 Cov.: 33 AF XY: 0.0533 AC XY: 3971 AN XY: 74468

African (AFR) AF: 0.0242 AC: 1007 AN: 41588

American (AMR) AF: 0.0789 AC: 1206 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.0680 AC: 236 AN: 3472

East Asian (EAS) AF: 0.222 AC: 1147 AN: 5172

South Asian (SAS) AF: 0.202 AC: 975 AN: 4824

European-Finnish (FIN) AF: 0.0328 AC: 348 AN: 10614

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.0367 AC: 2500 AN: 68036

Other (OTH) AF: 0.0605 AC: 128 AN: 2116

Alfa AF: 0.0398 Hom.: 79

Bravo AF: 0.0479

Asia WGS AF: 0.261 AC: 907 AN: 3478

EpiCase AF: 0.0388

EpiControl AF: 0.0359

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	5	not specified (5)
-	-	3	Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (3)
-	-	3	not provided (3)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.60
CADD	Benign	12
DANN	Benign	0.87
PhyloP100		1.4
Mutation Taster		=98/2	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: rs61742664; hg19: chr19-36549684; COSMIC: COSV99495663; COSMIC: COSV99495663;