rs17851502

Variant names:

• chr19-36103161-C-T
• rs17851502
• NM_001083961.2:c.3468C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-36103161-C-T
• chr19-36103161-C-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.3468C>T​(p.Leu1156Leu) 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 1,613,930 control chromosomes in the GnomAD database, including 10,318 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.14 (1724 hom., cov: 33)
  • Exomes 𝑓: 0.10 (8594 hom.)
• Consequence: WDR62 NM_001083961.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: -1.94
• Publications: 9 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 -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 19-36103161-C-T is Benign according to our data. Variant chr19-36103161-C-T is described in ClinVar as Benign. ClinVar VariationId is 160287.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-1.94 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 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.3468C>T	p.Leu1156Leu	synonymous	Exon 29 of 32	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.3453C>T	p.Leu1151Leu	synonymous	Exon 29 of 32	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.3453C>T	p.Leu1151Leu	synonymous	Exon 29 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.3468C>T	p.Leu1156Leu	synonymous	Exon 29 of 32	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.*3328C>T		non_coding_transcript_exon	Exon 27 of 30	ENSP00000465525.1	O43379-2
	WDR62	ENST00000587391.6	TSL:1	n.*3328C>T		3_prime_UTR	Exon 27 of 30	ENSP00000465525.1	O43379-2

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20728 AN: 152070 Hom.: 1724 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.119

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.000772

Gnomad SAS AF: 0.0893

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.155

GnomAD2 exomes AF: 0.104 AC: 26021 AN: 250954 AF XY: 0.104

Gnomad AFR exome AF: 0.227

Gnomad AMR exome AF: 0.0733

Gnomad ASJ exome AF: 0.129

Gnomad EAS exome AF: 0.000163

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.111

Gnomad OTH exome AF: 0.118

GnomAD4 exome AF: 0.104 AC: 151692 AN: 1461742 Hom.: 8594 Cov.: 34 AF XY: 0.104 AC XY: 75685 AN XY: 727176

African (AFR) AF: 0.227 AC: 7616 AN: 33480

American (AMR) AF: 0.0771 AC: 3446 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.123 AC: 3205 AN: 26136

East Asian (EAS) AF: 0.000428 AC: 17 AN: 39698

South Asian (SAS) AF: 0.0912 AC: 7863 AN: 86254

European-Finnish (FIN) AF: 0.109 AC: 5822 AN: 53290

Middle Eastern (MID) AF: 0.193 AC: 1114 AN: 5768

European-Non Finnish (NFE) AF: 0.104 AC: 115846 AN: 1112004

Other (OTH) AF: 0.112 AC: 6763 AN: 60394

GnomAD4 genome AF: 0.136 AC: 20741 AN: 152188 Hom.: 1724 Cov.: 33 AF XY: 0.135 AC XY: 10052 AN XY: 74406

African (AFR) AF: 0.224 AC: 9281 AN: 41516

American (AMR) AF: 0.106 AC: 1627 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 456 AN: 3470

East Asian (EAS) AF: 0.000773 AC: 4 AN: 5172

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

European-Finnish (FIN) AF: 0.116 AC: 1227 AN: 10606

Middle Eastern (MID) AF: 0.248 AC: 73 AN: 294

European-Non Finnish (NFE) AF: 0.106 AC: 7211 AN: 67982

Other (OTH) AF: 0.153 AC: 323 AN: 2112

Alfa AF: 0.118 Hom.: 2112

Bravo AF: 0.141

Asia WGS AF: 0.0510 AC: 180 AN: 3478

EpiCase AF: 0.123

EpiControl AF: 0.130

ClinVar

ClinVar submissions

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	-0.75
CADD	Benign	2.1
DANN	Benign	0.42
PhyloP100		-1.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: rs17851502; hg19: chr19-36594063;