rs192260189

Variant names:

• chr9-215081-T-C
• rs192260189
• NM_203447.4:c.53+52T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-215081-T-C
• chr9-215081-T-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_203447.4(DOCK8):​c.53+52T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000724 in 1,380,638 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: 32)
  • Exomes 𝑓: 7.2e-7 (0 hom.)
• Consequence: DOCK8 NM_203447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.56
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.046586037).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK8	NM_203447.4	c.53+52T>C		intron_variant	Intron 1 of 47	ENST00000432829.7	NP_982272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7	c.53+52T>C		intron_variant	Intron 1 of 47	1	NM_203447.4	ENSP00000394888.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.24e-7 AC: 1 AN: 1380638 Hom.: 0 Cov.: 45 AF XY: 0.00 AC XY: 0 AN XY: 682630

African (AFR) AF: 0.00 AC: 0 AN: 28960

American (AMR) AF: 0.00 AC: 0 AN: 35838

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24486

East Asian (EAS) AF: 0.00 AC: 0 AN: 34280

South Asian (SAS) AF: 0.00 AC: 0 AN: 78760

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 35198

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5104

European-Non Finnish (NFE) AF: 9.26e-7 AC: 1 AN: 1080452

Other (OTH) AF: 0.00 AC: 0 AN: 57560

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.41	T
BayesDel_noAF	Benign	-0.83
CADD	Benign	3.9
DANN	Benign	0.26
DEOGEN2	Benign	0.044	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.4
FATHMM_MKL	Benign	0.011	N
LIST_S2	Benign	0.15	T
M_CAP	Benign	0.0012	T
MetaRNN	Benign	0.047	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	N
PhyloP100		-2.6
PROVEAN	Benign	0.75	N
REVEL	Benign	0.030
Sift4G	Benign	0.64	T
Polyphen		0.0	B
Vest4		0.020
MutPred		0.090		Loss of loop (P = 0.0374);
MVP		0.061
MPC		0.13
ClinPred		0.053	T
GERP RS		-0.70
PromoterAI		0.12	Neutral
Varity_R		0.073
gMVP		0.022

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: rs192260189; hg19: chr9-215081; COSMIC: COSV66688182; COSMIC: COSV66688182;