19-36073544-C-T

Variant names:

• chr19-36073544-C-T
• rs76130844
• NM_001083961.2:c.1233+13C>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.1233+13C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0427 in 1,461,698 control chromosomes in the GnomAD database, including 1,604 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.036 (145 hom., cov: 31)
  • Exomes 𝑓: 0.043 (1459 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:8
• Conservation: PhyloP100: -1.55
• Publications: 4 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 19-36073544-C-T is Benign according to our data. Variant chr19-36073544-C-T is described in ClinVar as Benign. ClinVar VariationId is 160245.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.105 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.1233+13C>T		intron	N/A	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.1218+13C>T		intron	N/A	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.1233+13C>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.1233+13C>T		intron	N/A	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.1233+13C>T		intron	N/A	ENSP00000465525.1	O43379-2
	WDR62	ENST00000679714.1		c.1227+19C>T		intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5369 AN: 149890 Hom.: 142 Cov.: 31

Gnomad AFR AF: 0.0218

Gnomad AMI AF: 0.00887

Gnomad AMR AF: 0.0286

Gnomad ASJ AF: 0.0649

Gnomad EAS AF: 0.112

Gnomad SAS AF: 0.0810

Gnomad FIN AF: 0.0318

Gnomad MID AF: 0.0417

Gnomad NFE AF: 0.0364

Gnomad OTH AF: 0.0414

GnomAD2 exomes AF: 0.0489 AC: 11518 AN: 235362 AF XY: 0.0503

Gnomad AFR exome AF: 0.0265

Gnomad AMR exome AF: 0.0209

Gnomad ASJ exome AF: 0.0673

Gnomad EAS exome AF: 0.125

Gnomad FIN exome AF: 0.0341

Gnomad NFE exome AF: 0.0398

Gnomad OTH exome AF: 0.0485

GnomAD4 exome AF: 0.0435 AC: 56995 AN: 1311696 Hom.: 1459 Cov.: 31 AF XY: 0.0447 AC XY: 29326 AN XY: 656216

African (AFR) AF: 0.0232 AC: 708 AN: 30532

American (AMR) AF: 0.0225 AC: 968 AN: 43034

Ashkenazi Jewish (ASJ) AF: 0.0732 AC: 1776 AN: 24270

East Asian (EAS) AF: 0.113 AC: 4134 AN: 36536

South Asian (SAS) AF: 0.0784 AC: 6520 AN: 83182

European-Finnish (FIN) AF: 0.0370 AC: 1721 AN: 46548

Middle Eastern (MID) AF: 0.0490 AC: 264 AN: 5392

European-Non Finnish (NFE) AF: 0.0385 AC: 38001 AN: 987626

Other (OTH) AF: 0.0532 AC: 2903 AN: 54576

GnomAD4 genome AF: 0.0359 AC: 5380 AN: 150002 Hom.: 145 Cov.: 31 AF XY: 0.0362 AC XY: 2649 AN XY: 73222

African (AFR) AF: 0.0218 AC: 896 AN: 41120

American (AMR) AF: 0.0286 AC: 433 AN: 15152

Ashkenazi Jewish (ASJ) AF: 0.0649 AC: 222 AN: 3420

East Asian (EAS) AF: 0.112 AC: 566 AN: 5044

South Asian (SAS) AF: 0.0807 AC: 380 AN: 4708

European-Finnish (FIN) AF: 0.0318 AC: 324 AN: 10194

Middle Eastern (MID) AF: 0.0448 AC: 13 AN: 290

European-Non Finnish (NFE) AF: 0.0364 AC: 2443 AN: 67098

Other (OTH) AF: 0.0458 AC: 95 AN: 2074

Alfa AF: 0.0248 Hom.: 16

Bravo AF: 0.0338

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	4	not specified (4)
-	-	2	Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (2)
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	0.28
DANN	Benign	0.69
PhyloP100		-1.6
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: rs76130844; hg19: chr19-36564446; COSMIC: COSV54332745; COSMIC: COSV54332745;