rs4806263

Variant names:

• chr19-36086677-C-T
• rs4806263
• NM_001083961.2:c.1643-10C>T

Your query was ambiguous. Multiple possible variants found:

• chr19-36086677-C-T
• chr19-36086677-C-G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001083961.2(WDR62):​c.1643-10C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.107 in 1,594,750 control chromosomes in the GnomAD database, including 10,145 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: 31)
  • Exomes 𝑓: 0.10 (8421 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Scores: Splicing: ADA: 0.00001701
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:11
• Conservation: PhyloP100: 0.314
• Publications: 6 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 19-36086677-C-T is Benign according to our data. Variant chr19-36086677-C-T is described in ClinVar as Benign. ClinVar VariationId is 160253.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.219 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.1643-10C>T		intron	N/A	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.1628-10C>T		intron	N/A	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.1643-10C>T		intron	N/A	NP_775907.4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	WDR62	ENST00000401500.7	TSL:1 MANE Select	c.1643-10C>T		intron	N/A	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.*333-10C>T		intron	N/A	ENSP00000465525.1	O43379-2
	WDR62	ENST00000679714.1		c.1637-10C>T		intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20710 AN: 152056 Hom.: 1724 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.118

Gnomad AMR AF: 0.107

Gnomad ASJ AF: 0.132

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0890

Gnomad FIN AF: 0.116

Gnomad MID AF: 0.241

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.154

GnomAD2 exomes AF: 0.100 AC: 22190 AN: 220914 AF XY: 0.101

Gnomad AFR exome AF: 0.219

Gnomad AMR exome AF: 0.0727

Gnomad ASJ exome AF: 0.128

Gnomad EAS exome AF: 0.000176

Gnomad FIN exome AF: 0.113

Gnomad NFE exome AF: 0.107

Gnomad OTH exome AF: 0.117

GnomAD4 exome AF: 0.104 AC: 149311 AN: 1442576 Hom.: 8421 Cov.: 33 AF XY: 0.104 AC XY: 74292 AN XY: 715818

African (AFR) AF: 0.227 AC: 7507 AN: 32998

American (AMR) AF: 0.0766 AC: 3261 AN: 42590

Ashkenazi Jewish (ASJ) AF: 0.122 AC: 3129 AN: 25718

East Asian (EAS) AF: 0.000436 AC: 17 AN: 38980

South Asian (SAS) AF: 0.0916 AC: 7643 AN: 83458

European-Finnish (FIN) AF: 0.109 AC: 5624 AN: 51802

Middle Eastern (MID) AF: 0.194 AC: 1115 AN: 5752

European-Non Finnish (NFE) AF: 0.104 AC: 114351 AN: 1101686

Other (OTH) AF: 0.112 AC: 6664 AN: 59592

GnomAD4 genome AF: 0.136 AC: 20723 AN: 152174 Hom.: 1724 Cov.: 31 AF XY: 0.135 AC XY: 10038 AN XY: 74426

African (AFR) AF: 0.223 AC: 9262 AN: 41492

American (AMR) AF: 0.107 AC: 1629 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.132 AC: 459 AN: 3470

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5182

South Asian (SAS) AF: 0.0891 AC: 429 AN: 4816

European-Finnish (FIN) AF: 0.116 AC: 1228 AN: 10604

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

European-Non Finnish (NFE) AF: 0.106 AC: 7209 AN: 68006

Other (OTH) AF: 0.153 AC: 323 AN: 2114

Alfa AF: 0.122 Hom.: 913

Bravo AF: 0.141

Asia WGS AF: 0.0520 AC: 182 AN: 3478

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	-0.81
CADD	Benign	5.0
DANN	Benign	0.58
PhyloP100		0.31
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000017
dbscSNV1_RF	Benign	0.0040
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: rs4806263; hg19: chr19-36577579;