chr19-36073537-CC-CCCCCCCCC

Variant names:

• chr19-36073536-G-GCCCCCCC
• NM_001083961.2:c.1233+9_1233+15dupCCCCCCC

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000401500.7(WDR62):​c.1233+5_1233+6insCCCCCCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.00020 (0 hom., cov: 31)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: WDR62 ENST00000401500.7 splice_region, intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.491
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000401500.7. 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+9_1233+15dupCCCCCCC		intron	N/A	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.1218+9_1218+15dupCCCCCCC		intron	N/A	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.1233+9_1233+15dupCCCCCCC		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+5_1233+6insCCCCCCC		splice_region intron	N/A	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.1233+5_1233+6insCCCCCCC		splice_region intron	N/A	ENSP00000465525.1	O43379-2
	WDR62	ENST00000679714.1		c.1227+11_1227+12insCCCCCCC		intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes AF: 0.000205 AC: 30 AN: 146582 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000126

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000683

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000397

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.000101

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000287

Gnomad OTH AF: 0.000496

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 1157924 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 582008

African (AFR) AF: 0.00 AC: 0 AN: 27552

American (AMR) AF: 0.00 AC: 0 AN: 40094

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21434

East Asian (EAS) AF: 0.00 AC: 0 AN: 32234

South Asian (SAS) AF: 0.00 AC: 0 AN: 79244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 43550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4870

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 860920

Other (OTH) AF: 0.00 AC: 0 AN: 48026

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000205 AC: 30 AN: 146582 Hom.: 0 Cov.: 31 AF XY: 0.000154 AC XY: 11 AN XY: 71248

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000126 AC: 5 AN: 39566

American (AMR) AF: 0.0000683 AC: 1 AN: 14648

Ashkenazi Jewish (ASJ) AF: 0.000293 AC: 1 AN: 3410

East Asian (EAS) AF: 0.000397 AC: 2 AN: 5034

South Asian (SAS) AF: 0.00 AC: 0 AN: 4572

European-Finnish (FIN) AF: 0.000101 AC: 1 AN: 9904

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 306

European-Non Finnish (NFE) AF: 0.000287 AC: 19 AN: 66224

Other (OTH) AF: 0.000496 AC: 1 AN: 2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.49

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr19-36564438;