Genetic Variant DOCK8:c.-152+3531A>T (chr9-214847-A-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NR_160804.1(DOCK8-AS1):n.904T>A variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000138 in 1,449,514 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 34)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DOCK8-AS1
NR_160804.1 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.78

Publications

1 publications found

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:26436): (DOCK8 antisense RNA 1)

DOCK8-AS1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.25041163).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NR_160804.1. 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
	DOCK8-AS1	NR_160804.1		n.904T>A		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	NM_203447.4	MANE Select	c.-130A>T		upstream_gene	N/A	NP_982272.2	Q8NF50-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK8-AS1	ENST00000382387.4	TSL:6	n.1047T>A	non_coding_transcript_exon	Exon 1 of 1
DOCK8-AS1	ENST00000648587.1		n.895T>A	non_coding_transcript_exon	Exon 1 of 1
DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-130A>T	upstream_gene	N/A	ENSP00000394888.3	Q8NF50-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000430

AC:

AN:

232618

AF XY:

0.00000780

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000959

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000138

AC:

AN:

1449514

Hom.:

Cov.:

AF XY:

0.00000139

AC XY:

AN XY:

721104

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32122

American (AMR)

AF:

0.00

AC:

AN:

44010

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25800

East Asian (EAS)

AF:

0.00

AC:

AN:

38786

South Asian (SAS)

AF:

0.00

AC:

AN:

84822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51858

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5738

European-Non Finnish (NFE)

AF:

9.04e-7

AC:

AN:

1106396

Other (OTH)

AF:

0.0000167

AC:

AN:

59982

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000849

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.23

BayesDel_noAF

Benign

-0.56

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.0095

Eigen

Uncertain

0.34

Eigen_PC

Uncertain

0.37

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.33

M_CAP

Benign

0.054

MetaRNN

Benign

0.25

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

PhyloP100

2.8

PROVEAN

Uncertain

-2.6

REVEL

Benign

0.17

Sift4G

Benign

0.83

Polyphen

1.0

Vest4

0.45

MutPred

0.075

Loss of phosphorylation at S184 (P = 0.048)

MVP

0.25

MPC

0.22

ClinPred

0.53

GERP RS

4.9

PromoterAI

-0.79

Under-expression

(source)

Varity_R

0.64

gMVP

0.016

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over