chr9-212421-T-G

Variant names:

• chr9-212421-T-G
• rs493348
• XM_047423927.1:c.-152+1105T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The XM_047423927.1(DOCK8):​c.-152+1105T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.27 in 151,884 control chromosomes in the GnomAD database, including 5,670 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.27 (5670 hom., cov: 32)
• Consequence: DOCK8 XM_047423927.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -5.37
• Publications: 1 publications found

Genes affected

DOCK8 (HGNC:19191): (dedicator of cytokinesis 8) This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

DOCK8 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to DOCK8 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.306 is higher than 0.05.

Variant Effect in Transcripts

 

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Frequencies

GnomAD3 genomes AF: 0.270 AC: 40989 AN: 151766 Hom.: 5667 Cov.: 32

Gnomad AFR AF: 0.214

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.268

Gnomad ASJ AF: 0.187

Gnomad EAS AF: 0.319

Gnomad SAS AF: 0.255

Gnomad FIN AF: 0.306

Gnomad MID AF: 0.268

Gnomad NFE AF: 0.300

Gnomad OTH AF: 0.283

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.270 AC: 41007 AN: 151884 Hom.: 5670 Cov.: 32 AF XY: 0.272 AC XY: 20166 AN XY: 74208

African (AFR) AF: 0.213 AC: 8835 AN: 41404

American (AMR) AF: 0.267 AC: 4086 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.187 AC: 649 AN: 3470

East Asian (EAS) AF: 0.319 AC: 1642 AN: 5146

South Asian (SAS) AF: 0.257 AC: 1236 AN: 4818

European-Finnish (FIN) AF: 0.306 AC: 3220 AN: 10524

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.300 AC: 20401 AN: 67932

Other (OTH) AF: 0.279 AC: 589 AN: 2108

Alfa AF: 0.166 Hom.: 455

Bravo AF: 0.269

Asia WGS AF: 0.263 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.062
DANN	Benign	0.50
PhyloP100		-5.4

Splicing

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

Other links and lift over

dbSNP: rs493348; hg19: chr9-212421; COSMIC: COSV66688439;