19-36083161-C-T

Variant names:

• chr19-36083161-C-T
• rs45567532
• NM_001083961.2:c.1470C>T

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.1470C>T​(p.Asp490Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,612,408 control chromosomes in the GnomAD database, including 10,490 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1862 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8628 hom.)
• Consequence: WDR62 NM_001083961.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:10
• Conservation: PhyloP100: -0.840
• Publications: 8 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=-0.67).
• BP6: Variant 19-36083161-C-T is Benign according to our data. Variant chr19-36083161-C-T is described in ClinVar as Benign. ClinVar VariationId is 160248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.84 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.232 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.1470C>T	p.Asp490Asp	synonymous	Exon 11 of 32	NP_001077430.1
	WDR62	NM_001411145.1		c.1455C>T	p.Asp485Asp	synonymous	Exon 11 of 32	NP_001398074.1
	WDR62	NM_173636.5		c.1470C>T	p.Asp490Asp	synonymous	Exon 11 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.1470C>T	p.Asp490Asp	synonymous	Exon 11 of 32	ENSP00000384792.1
	WDR62	ENST00000587391.6	TSL:1	n.*160C>T		non_coding_transcript_exon	Exon 12 of 30	ENSP00000465525.1
	WDR62	ENST00000587391.6	TSL:1	n.*160C>T		3_prime_UTR	Exon 12 of 30	ENSP00000465525.1

Frequencies

GnomAD3 genomes AF: 0.140 AC: 21299 AN: 152066 Hom.: 1862 Cov.: 33

Gnomad AFR AF: 0.236

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.109

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.242

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.160

GnomAD2 exomes AF: 0.103 AC: 25497 AN: 247800 AF XY: 0.103

Gnomad AFR exome AF: 0.237

Gnomad AMR exome AF: 0.0738

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.112

Gnomad NFE exome AF: 0.108

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.104 AC: 151886 AN: 1460224 Hom.: 8628 Cov.: 33 AF XY: 0.104 AC XY: 75720 AN XY: 726192

African (AFR) AF: 0.240 AC: 8033 AN: 33450

American (AMR) AF: 0.0777 AC: 3460 AN: 44532

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3190 AN: 26080

East Asian (EAS) AF: 0.000454 AC: 18 AN: 39688

South Asian (SAS) AF: 0.0914 AC: 7852 AN: 85942

European-Finnish (FIN) AF: 0.109 AC: 5803 AN: 53312

Middle Eastern (MID) AF: 0.194 AC: 1116 AN: 5766

European-Non Finnish (NFE) AF: 0.104 AC: 115599 AN: 1111136

Other (OTH) AF: 0.113 AC: 6815 AN: 60318

GnomAD4 genome AF: 0.140 AC: 21315 AN: 152184 Hom.: 1862 Cov.: 33 AF XY: 0.139 AC XY: 10312 AN XY: 74422

African (AFR) AF: 0.236 AC: 9792 AN: 41508

American (AMR) AF: 0.109 AC: 1670 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3472

East Asian (EAS) AF: 0.000771 AC: 4 AN: 5188

South Asian (SAS) AF: 0.0893 AC: 431 AN: 4824

European-Finnish (FIN) AF: 0.116 AC: 1222 AN: 10578

Middle Eastern (MID) AF: 0.250 AC: 73 AN: 292

European-Non Finnish (NFE) AF: 0.106 AC: 7222 AN: 68002

Other (OTH) AF: 0.158 AC: 334 AN: 2116

Alfa AF: 0.108 Hom.: 540

Bravo AF: 0.145

Asia WGS AF: 0.0540 AC: 190 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	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	-0.67
CADD	Benign	3.6
DANN	Benign	0.60
PhyloP100		-0.84
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs45567532; hg19: chr19-36574063; COSMIC: COSV54335313;