chr9-212421-T-G

Position:

• chr9-212421-T-G

Variant summary

Our verdict is Benign. Variant got -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

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK8	XM_047423927.1	c.-152+1105T>G		intron_variant			XP_047279883.1
DOCK8	XM_017015173.2	c.-152+1105T>G		intron_variant			XP_016870662.1
DOCK8	XM_047423930.1	c.-152+1105T>G		intron_variant			XP_047279886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt

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

Gnomad4 AFR AF: 0.213

Gnomad4 AMR AF: 0.267

Gnomad4 ASJ AF: 0.187

Gnomad4 EAS AF: 0.319

Gnomad4 SAS AF: 0.257

Gnomad4 FIN AF: 0.306

Gnomad4 NFE AF: 0.300

Gnomad4 OTH AF: 0.279

Alfa AF: 0.165 Hom.: 439

Bravo AF: 0.269

Asia WGS AF: 0.263 AC: 912 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Splicing

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

Publications

LitVar

Other links and lift over

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