19-36073536-GCCC-GCCCCC

Variant names:

• chr19-36073536-G-GCC
• rs373693641
• NM_001083961.2:c.1233+14_1233+15dupCC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000401500.7(WDR62):​c.1233+5_1233+6insCC variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000583 in 1,303,884 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00016 (0 hom., cov: 31)
  • Exomes 𝑓: 0.000045 (0 hom.)
• Consequence: WDR62 ENST00000401500.7 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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), Laboratory for Molecular Medicine, ClinGen, G2P, Illumina, Ambry Genetics
• autosomal recessive primary microcephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 19-36073536-G-GCC is Benign according to our data. Variant chr19-36073536-G-GCC is described in ClinVar as Benign. ClinVar VariationId is 1541176.Status of the report is criteria_provided_single_submitter, 1 stars.

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+14_1233+15dupCC		intron	N/A	NP_001077430.1	O43379-4
	WDR62	NM_001411145.1		c.1218+14_1218+15dupCC		intron	N/A	NP_001398074.1	A0A7P0TAK3
	WDR62	NM_173636.5		c.1233+14_1233+15dupCC		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+6insCC		splice_region intron	N/A	ENSP00000384792.1	O43379-4
	WDR62	ENST00000587391.6	TSL:1	n.1233+5_1233+6insCC		splice_region intron	N/A	ENSP00000465525.1	O43379-2
	WDR62	ENST00000679714.1		c.1227+11_1227+12insCC		intron	N/A	ENSP00000506627.1	A0A7P0TBE7

Frequencies

GnomAD3 genomes AF: 0.000164 AC: 24 AN: 146590 Hom.: 0 Cov.: 31

Gnomad AFR AF: 0.000278

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000219

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000151

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000449 AC: 52 AN: 1157294 Hom.: 0 Cov.: 28 AF XY: 0.0000602 AC XY: 35 AN XY: 581710

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

African (AFR) AF: 0.000400 AC: 11 AN: 27522

American (AMR) AF: 0.0000499 AC: 2 AN: 40078

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 21418

East Asian (EAS) AF: 0.000496 AC: 16 AN: 32226

South Asian (SAS) AF: 0.0000252 AC: 2 AN: 79246

European-Finnish (FIN) AF: 0.0000459 AC: 2 AN: 43544

Middle Eastern (MID) AF: 0.000205 AC: 1 AN: 4868

European-Non Finnish (NFE) AF: 0.0000209 AC: 18 AN: 860392

Other (OTH) AF: 0.00 AC: 0 AN: 48000

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000164 AC: 24 AN: 146590 Hom.: 0 Cov.: 31 AF XY: 0.000126 AC XY: 9 AN XY: 71254

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

African (AFR) AF: 0.000278 AC: 11 AN: 39558

American (AMR) AF: 0.00 AC: 0 AN: 14648

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

East Asian (EAS) AF: 0.00 AC: 0 AN: 5034

South Asian (SAS) AF: 0.000219 AC: 1 AN: 4570

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9908

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

European-Non Finnish (NFE) AF: 0.000151 AC: 10 AN: 66238

Other (OTH) AF: 0.00 AC: 0 AN: 2018

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.000000000100515), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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

dbSNP: rs373693641;

hg19: chr19-36564438;