Genetic Variant DOCK8:c.-12C>T (chr9-214965-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_203447.4(DOCK8):c.-12C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000749 in 1,602,070 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DOCK8
NM_203447.4 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.202

Publications

0 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.58).

BP6

Variant 9-214965-C-T is Benign according to our data. Variant chr9-214965-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 512917.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203447.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK8	NM_203447.4	MANE Select	c.-12C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 48	NP_982272.2	Q8NF50-1
DOCK8	NM_203447.4	MANE Select	c.-12C>T	5_prime_UTR	Exon 1 of 48	NP_982272.2	Q8NF50-1
DOCK8-AS1	NR_160804.1		n.786G>A	non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-12C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 48	ENSP00000394888.3	Q8NF50-1
DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-12C>T	5_prime_UTR	Exon 1 of 48	ENSP00000394888.3	Q8NF50-1
DOCK8	ENST00000469197.5	TSL:5	n.-12C>T	5_prime_UTR_premature_start_codon_gain	Exon 1 of 5	ENSP00000418587.1	F8WC95

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152176

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000911

AC:

AN:

219540

AF XY:

0.0000163

show subpopulations

Gnomad AFR exome

AF:

0.000183

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000552

AC:

AN:

1449894

Hom.:

Cov.:

109

AF XY:

0.00000971

AC XY:

AN XY:

721136

show subpopulations

African (AFR)

AF:

0.000188

AC:

AN:

31992

American (AMR)

AF:

0.00

AC:

AN:

44006

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25802

East Asian (EAS)

AF:

0.00

AC:

AN:

38858

South Asian (SAS)

AF:

0.0000118

AC:

AN:

84910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50056

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5722

European-Non Finnish (NFE)

AF:

9.02e-7

AC:

AN:

1108668

Other (OTH)

AF:

0.00

AC:

AN:

59880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.519

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

AF:

0.0000263

AC:

AN:

152176

Hom.:

Cov.:

AF XY:

0.0000404

AC XY:

AN XY:

74340

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41444

American (AMR)

AF:

0.00

AC:

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4834

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.00

AC:

AN:

314

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68020

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000264

ClinVar

ClinVar submissions as Germline

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.58

CADD

Benign

7.4

(source)

DANN

Benign

0.85

PhyloP100

-0.20

PromoterAI

-0.035

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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