19-36067810-C-T

Variant names:

• chr19-36067810-C-T
• rs10423651
• NM_001083961.2:c.700-18C>T

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.700-18C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.302 in 1,612,366 control chromosomes in the GnomAD database, including 75,105 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.28 (6431 hom., cov: 33)
  • Exomes 𝑓: 0.30 (68674 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:9
• Conservation: PhyloP100: 0.403
• Publications: 5 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=-0.82).
• BP6: Variant 19-36067810-C-T is Benign according to our data. Variant chr19-36067810-C-T is described in ClinVar as Benign. ClinVar VariationId is 137906.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.322 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.700-18C>T		intron	N/A	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.700-18C>T		intron	N/A	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.700-18C>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.700-18C>T		intron	N/A	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.700-18C>T		intron	N/A	ENSP00000465525.1	O43379-2
	WDR62	ENST00000679714.1		c.700-18C>T		intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43251 AN: 152052 Hom.: 6434 Cov.: 33

Gnomad AFR AF: 0.226

Gnomad AMI AF: 0.148

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.289

Gnomad EAS AF: 0.267

Gnomad SAS AF: 0.181

Gnomad FIN AF: 0.340

Gnomad MID AF: 0.266

Gnomad NFE AF: 0.325

Gnomad OTH AF: 0.285

GnomAD2 exomes AF: 0.281 AC: 70000 AN: 249524 AF XY: 0.280

Gnomad AFR exome AF: 0.229

Gnomad AMR exome AF: 0.237

Gnomad ASJ exome AF: 0.291

Gnomad EAS exome AF: 0.268

Gnomad FIN exome AF: 0.330

Gnomad NFE exome AF: 0.320

Gnomad OTH exome AF: 0.282

GnomAD4 exome AF: 0.304 AC: 443509 AN: 1460198 Hom.: 68674 Cov.: 36 AF XY: 0.301 AC XY: 218457 AN XY: 726472

African (AFR) AF: 0.228 AC: 7630 AN: 33450

American (AMR) AF: 0.236 AC: 10563 AN: 44696

Ashkenazi Jewish (ASJ) AF: 0.288 AC: 7535 AN: 26124

East Asian (EAS) AF: 0.290 AC: 11519 AN: 39698

South Asian (SAS) AF: 0.185 AC: 15923 AN: 86216

European-Finnish (FIN) AF: 0.333 AC: 17668 AN: 53050

Middle Eastern (MID) AF: 0.234 AC: 1253 AN: 5348

European-Non Finnish (NFE) AF: 0.319 AC: 354201 AN: 1111310

Other (OTH) AF: 0.285 AC: 17217 AN: 60306

GnomAD4 genome AF: 0.284 AC: 43266 AN: 152168 Hom.: 6431 Cov.: 33 AF XY: 0.283 AC XY: 21021 AN XY: 74394

African (AFR) AF: 0.226 AC: 9387 AN: 41520

American (AMR) AF: 0.268 AC: 4092 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.289 AC: 1002 AN: 3470

East Asian (EAS) AF: 0.266 AC: 1378 AN: 5180

South Asian (SAS) AF: 0.180 AC: 869 AN: 4822

European-Finnish (FIN) AF: 0.340 AC: 3598 AN: 10584

Middle Eastern (MID) AF: 0.259 AC: 76 AN: 294

European-Non Finnish (NFE) AF: 0.325 AC: 22127 AN: 67984

Other (OTH) AF: 0.284 AC: 602 AN: 2116

Alfa AF: 0.304 Hom.: 1186

Bravo AF: 0.275

Asia WGS AF: 0.204 AC: 708 AN: 3478

ClinVar

ClinVar submissions

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)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	9.9
DANN	Benign	0.74
PhyloP100		0.40
RBP_binding_hub_radar		0.67
RBP_regulation_power_radar		1.8
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: rs10423651; hg19: chr19-36558712; COSMIC: COSV54335661; COSMIC: COSV54335661;