rs61740165

Variant names:

• chr19-36105033-G-A
• rs61740165
• NM_001083961.2:c.*5G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_001083961.2(WDR62):​c.*5G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00277 in 1,591,074 control chromosomes in the GnomAD database, including 183 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0075 (55 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (128 hom.)
• Consequence: WDR62 NM_001083961.2 3_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:3
• Conservation: PhyloP100: 0.0900
• Publications: 1 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), Illumina, Ambry Genetics, Laboratory for Molecular Medicine, G2P, ClinGen
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BP6: Variant 19-36105033-G-A is Benign according to our data. Variant chr19-36105033-G-A is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 160242.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0658 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.*5G>A		3_prime_UTR	Exon 32 of 32	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.*5G>A		3_prime_UTR	Exon 32 of 32	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.*5G>A		3_prime_UTR	Exon 32 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.*5G>A		3_prime_UTR	Exon 32 of 32	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.*4437G>A		non_coding_transcript_exon	Exon 30 of 30	ENSP00000465525.1	O43379-2
	WDR62	ENST00000587391.6	TSL:1	n.*4437G>A		3_prime_UTR	Exon 30 of 30	ENSP00000465525.1	O43379-2

Frequencies

GnomAD3 genomes AF: 0.00755 AC: 1136 AN: 150436 Hom.: 55 Cov.: 32

Gnomad AFR AF: 0.00121

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0694

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000735

Gnomad OTH AF: 0.0116

GnomAD2 exomes AF: 0.0100 AC: 2185 AN: 217572 AF XY: 0.00745

Gnomad AFR exome AF: 0.00100

Gnomad AMR exome AF: 0.0655

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000913

Gnomad OTH exome AF: 0.00731

GnomAD4 exome AF: 0.00227 AC: 3266 AN: 1440522 Hom.: 128 Cov.: 34 AF XY: 0.00199 AC XY: 1424 AN XY: 716292

African (AFR) AF: 0.000657 AC: 21 AN: 31948

American (AMR) AF: 0.0689 AC: 2973 AN: 43166

Ashkenazi Jewish (ASJ) AF: 0.0000387 AC: 1 AN: 25816

East Asian (EAS) AF: 0.0000507 AC: 2 AN: 39416

South Asian (SAS) AF: 0.0000709 AC: 6 AN: 84666

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43640

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.0000785 AC: 87 AN: 1108102

Other (OTH) AF: 0.00295 AC: 176 AN: 59642

GnomAD4 genome AF: 0.00755 AC: 1136 AN: 150552 Hom.: 55 Cov.: 32 AF XY: 0.00904 AC XY: 666 AN XY: 73664

African (AFR) AF: 0.00120 AC: 48 AN: 39892

American (AMR) AF: 0.0693 AC: 1057 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.000386 AC: 2 AN: 5176

South Asian (SAS) AF: 0.00 AC: 0 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000735 AC: 5 AN: 68004

Other (OTH) AF: 0.0115 AC: 24 AN: 2096

Alfa AF: 0.00197 Hom.: 2

Bravo AF: 0.0112

ClinVar

ClinVar submissions

Significance: Conflicting classifications of pathogenicity

Revision: criteria provided, conflicting classifications

Pathogenic	VUS	Benign	Condition
-	1	1	Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (2)
-	-	1	not provided (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	4.6
DANN	Benign	0.65
PhyloP100		0.090
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: rs61740165; hg19: chr19-36595935;