rs144097790

Variant names:

• chr9-214919-C-G
• rs144097790
• NM_203447.4:c.-58C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-214919-C-G
• chr9-214919-C-T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203447.4(DOCK8):​c.-58C>G variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000689 in 1,452,084 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: 6.9e-7 (0 hom.)
• Consequence: DOCK8 NM_203447.4 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00400
• 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: 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=0.19574353).

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.-58C>G		5_prime_UTR	Exon 1 of 48	NP_982272.2	Q8NF50-1
	DOCK8-AS1	NR_160804.1		n.832G>C		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.-58C>G		5_prime_UTR	Exon 1 of 48	ENSP00000394888.3	Q8NF50-1
	DOCK8-AS1	ENST00000382387.4	TSL:6	n.975G>C		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	ENST00000454469.6	TSL:2	n.52C>G		non_coding_transcript_exon	Exon 1 of 14

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 6.89e-7 AC: 1 AN: 1452084 Hom.: 0 Cov.: 111 AF XY: 0.00000138 AC XY: 1 AN XY: 722378

African (AFR) AF: 0.00 AC: 0 AN: 32034

American (AMR) AF: 0.00 AC: 0 AN: 43976

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25842

East Asian (EAS) AF: 0.00 AC: 0 AN: 38832

South Asian (SAS) AF: 0.00 AC: 0 AN: 85000

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51478

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5732

European-Non Finnish (NFE) AF: 9.02e-7 AC: 1 AN: 1109164

Other (OTH) AF: 0.00 AC: 0 AN: 60026

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	8.0
DANN	Benign	0.75
DEOGEN2	Benign	0.047	T
Eigen	Benign	-0.37
Eigen_PC	Benign	-0.50
FATHMM_MKL	Benign	0.10	N
LIST_S2	Benign	0.35	T
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.20	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		-0.0040
PROVEAN	Uncertain	-4.4	D
REVEL	Benign	0.11
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.18
MutPred		0.23		Gain of loop (P = 0.0045)
MVP		0.18
MPC		0.57
ClinPred		0.51	D
GERP RS		3.8
PromoterAI		0.096	Neutral
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2
Varity_R		0.74
gMVP		0.028

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: rs144097790; hg19: chr9-214919;