9-214908-T-C

Variant names:

• chr9-214908-T-C
• rs62533313
• NM_203447.4:c.-69T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_203447.4(DOCK8):​c.-69T>C variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0983 in 1,603,930 control chromosomes in the GnomAD database, including 8,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.097 (751 hom., cov: 34)
  • Exomes 𝑓: 0.098 (7462 hom.)
• Consequence: DOCK8 NM_203447.4 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: 0.571
• Publications: 8 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-AS1 (HGNC:26436): (DOCK8 antisense RNA 1)

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 9-214908-T-C is Benign according to our data. Variant chr9-214908-T-C is described in ClinVar as Benign. ClinVar VariationId is 366225.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.111 is higher than 0.05.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK8	NM_203447.4	MANE Select	c.-69T>C		5_prime_UTR	Exon 1 of 48	NP_982272.2	Q8NF50-1
	DOCK8-AS1	NR_160804.1		n.843A>G		non_coding_transcript_exon	Exon 1 of 1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-69T>C		5_prime_UTR	Exon 1 of 48	ENSP00000394888.3	Q8NF50-1
	DOCK8-AS1	ENST00000382387.4	TSL:6	n.986A>G		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	ENST00000454469.6	TSL:2	n.41T>C		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes AF: 0.0972 AC: 14781 AN: 152006 Hom.: 754 Cov.: 34

Gnomad AFR AF: 0.110

Gnomad AMI AF: 0.177

Gnomad AMR AF: 0.0752

Gnomad ASJ AF: 0.104

Gnomad EAS AF: 0.00309

Gnomad SAS AF: 0.119

Gnomad FIN AF: 0.0933

Gnomad MID AF: 0.0669

Gnomad NFE AF: 0.0998

Gnomad OTH AF: 0.0899

GnomAD2 exomes AF: 0.0905 AC: 20582 AN: 227434 AF XY: 0.0928

Gnomad AFR exome AF: 0.107

Gnomad AMR exome AF: 0.0670

Gnomad ASJ exome AF: 0.103

Gnomad EAS exome AF: 0.00162

Gnomad FIN exome AF: 0.0897

Gnomad NFE exome AF: 0.102

Gnomad OTH exome AF: 0.0891

GnomAD4 exome AF: 0.0984 AC: 142922 AN: 1451816 Hom.: 7462 Cov.: 111 AF XY: 0.0990 AC XY: 71510 AN XY: 722222

African (AFR) AF: 0.115 AC: 3679 AN: 32046

American (AMR) AF: 0.0669 AC: 2937 AN: 43904

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 2656 AN: 25846

East Asian (EAS) AF: 0.00193 AC: 75 AN: 38770

South Asian (SAS) AF: 0.118 AC: 10053 AN: 84954

European-Finnish (FIN) AF: 0.0868 AC: 4480 AN: 51622

Middle Eastern (MID) AF: 0.111 AC: 635 AN: 5736

European-Non Finnish (NFE) AF: 0.102 AC: 112790 AN: 1108926

Other (OTH) AF: 0.0936 AC: 5617 AN: 60012

GnomAD4 genome AF: 0.0972 AC: 14791 AN: 152114 Hom.: 751 Cov.: 34 AF XY: 0.0953 AC XY: 7089 AN XY: 74378

African (AFR) AF: 0.110 AC: 4552 AN: 41506

American (AMR) AF: 0.0753 AC: 1151 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.104 AC: 361 AN: 3466

East Asian (EAS) AF: 0.00310 AC: 16 AN: 5160

South Asian (SAS) AF: 0.119 AC: 574 AN: 4824

European-Finnish (FIN) AF: 0.0933 AC: 987 AN: 10582

Middle Eastern (MID) AF: 0.0616 AC: 18 AN: 292

European-Non Finnish (NFE) AF: 0.0998 AC: 6783 AN: 67964

Other (OTH) AF: 0.0889 AC: 188 AN: 2114

Alfa AF: 0.0996 Hom.: 595

Bravo AF: 0.0952

Asia WGS AF: 0.0560 AC: 194 AN: 3472

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)
-	-	1	Combined immunodeficiency due to DOCK8 deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	11
DANN	Benign	0.65
PhyloP100		0.57
PromoterAI		-0.037	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs62533313; hg19: chr9-214908; COSMIC: COSV66688142; COSMIC: COSV66688142;