Variant 9-214593-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The XM_047423927.1(DOCK8):c.-152+3277T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00453 in 1,613,982 control chromosomes in the GnomAD database, including 273 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.024 ( 140 hom., cov: 32)

Exomes 𝑓: 0.0025 ( 133 hom. )

Consequence

DOCK8
XM_047423927.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.479

Variant links:

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 links:

DOCK8-AS1 (HGNC:):

DOCK8-AS1 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 9-214593-T-C is Benign according to our data. Variant chr9-214593-T-C is described in ClinVar as [Benign]. Clinvar id is 1279302.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0799 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Protein	UniProt
DOCK8	XM_047423927.1 linkuse as main transcript	c.-152+3277T>C	intron_variant	XP_047279883.1
DOCK8	XM_017015173.2 linkuse as main transcript	c.-152+3277T>C	intron_variant	XP_016870662.1	Q8NF50-3
DOCK8	XM_047423930.1 linkuse as main transcript	c.-152+3277T>C	intron_variant	XP_047279886.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK8-AS1	ENST00000382387.4 linkuse as main transcript	n.1301A>G		non_coding_transcript_exon_variant	1/1	6
DOCK8-AS1	ENST00000648587.1 linkuse as main transcript	n.1149A>G		non_coding_transcript_exon_variant	1/1

Frequencies

GnomAD3 genomes

AF:

0.0236

AC:

3595

AN:

152144

Hom.:

137

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0820

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00811

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000368

Gnomad OTH

AF:

0.0216

GnomAD3 exomes

AF:

0.00589

AC:

1475

AN:

250244

Hom.:

AF XY:

0.00448

AC XY:

608

AN XY:

135572

show subpopulations

Gnomad AFR exome

AF:

0.0796

Gnomad AMR exome

AF:

0.00379

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000163

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000389

Gnomad OTH exome

AF:

0.00295

GnomAD4 exome

AF:

0.00253

AC:

3698

AN:

1461722

Hom.:

133

Cov.:

AF XY:

0.00221

AC XY:

1609

AN XY:

727172

show subpopulations

Gnomad4 AFR exome

AF:

0.0863

Gnomad4 AMR exome

AF:

0.00456

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000278

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000168

Gnomad4 OTH exome

AF:

0.00585

GnomAD4 genome

AF:

0.0237

AC:

3613

AN:

152260

Hom.:

140

Cov.:

AF XY:

0.0230

AC XY:

1713

AN XY:

74438

show subpopulations

Gnomad4 AFR

AF:

0.0822

Gnomad4 AMR

AF:

0.00810

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000368

Gnomad4 OTH

AF:

0.0213

Alfa

AF:

0.0103

Hom.:

Bravo

AF:

0.0269

Asia WGS

AF:

0.00520

AC:

AN:

3478

EpiCase

AF:

0.000436

EpiControl

AF:

0.000356

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

4.4

DANN

Benign

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over