19-36091368-G-A

Variant names:

• chr19-36091368-G-A
• rs2301736
• NM_001083961.2:c.2147-34G>A

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.2147-34G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.53 in 1,356,602 control chromosomes in the GnomAD database, including 163,932 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.42 (13623 hom., cov: 31)
  • Exomes 𝑓: 0.54 (150309 hom.)
• Consequence: WDR62 NM_001083961.2 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• Conservation: PhyloP100: 1.16
• Publications: 11 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 19-36091368-G-A is Benign according to our data. Variant chr19-36091368-G-A is described in ClinVar as Benign. ClinVar VariationId is 160261.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.57 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.2147-34G>A		intron	N/A	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.2132-34G>A		intron	N/A	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.2147-34G>A		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.2147-34G>A		intron	N/A	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.*837-34G>A		intron	N/A	ENSP00000465525.1	O43379-2
	WDR62	ENST00000679714.1		c.2141-34G>A		intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes AF: 0.424 AC: 62758 AN: 147900 Hom.: 13612 Cov.: 31

Gnomad AFR AF: 0.301

Gnomad AMI AF: 0.277

Gnomad AMR AF: 0.507

Gnomad ASJ AF: 0.371

Gnomad EAS AF: 0.589

Gnomad SAS AF: 0.319

Gnomad FIN AF: 0.528

Gnomad MID AF: 0.334

Gnomad NFE AF: 0.465

Gnomad OTH AF: 0.414

GnomAD2 exomes AF: 0.444 AC: 111328 AN: 250824 AF XY: 0.434

Gnomad AFR exome AF: 0.289

Gnomad AMR exome AF: 0.571

Gnomad ASJ exome AF: 0.376

Gnomad EAS exome AF: 0.555

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.450

Gnomad OTH exome AF: 0.429

GnomAD4 exome AF: 0.543 AC: 656258 AN: 1208572 Hom.: 150309 Cov.: 31 AF XY: 0.532 AC XY: 322784 AN XY: 607000

African (AFR) AF: 0.398 AC: 9666 AN: 24272

American (AMR) AF: 0.588 AC: 25271 AN: 42992

Ashkenazi Jewish (ASJ) AF: 0.459 AC: 9611 AN: 20930

East Asian (EAS) AF: 0.653 AC: 23416 AN: 35838

South Asian (SAS) AF: 0.317 AC: 25043 AN: 78888

European-Finnish (FIN) AF: 0.544 AC: 26232 AN: 48214

Middle Eastern (MID) AF: 0.380 AC: 1728 AN: 4544

European-Non Finnish (NFE) AF: 0.564 AC: 509804 AN: 904596

Other (OTH) AF: 0.528 AC: 25487 AN: 48298

GnomAD4 genome AF: 0.424 AC: 62794 AN: 148030 Hom.: 13623 Cov.: 31 AF XY: 0.427 AC XY: 30805 AN XY: 72160

African (AFR) AF: 0.301 AC: 12128 AN: 40338

American (AMR) AF: 0.508 AC: 7640 AN: 15040

Ashkenazi Jewish (ASJ) AF: 0.371 AC: 1265 AN: 3408

East Asian (EAS) AF: 0.588 AC: 2896 AN: 4926

South Asian (SAS) AF: 0.317 AC: 1363 AN: 4296

European-Finnish (FIN) AF: 0.528 AC: 5283 AN: 9998

Middle Eastern (MID) AF: 0.322 AC: 92 AN: 286

European-Non Finnish (NFE) AF: 0.465 AC: 31032 AN: 66802

Other (OTH) AF: 0.414 AC: 852 AN: 2060

Alfa AF: 0.433 Hom.: 6204

Bravo AF: 0.413

Asia WGS AF: 0.386 AC: 1340 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	2	not specified (2)
-	-	1	Microcephaly 2, primary, autosomal recessive, with or without cortical malformations (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	7.3
DANN	Benign	0.57
PhyloP100		1.2
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs2301736; hg19: chr19-36582270; COSMIC: COSV54332973;