9-214748-C-G

Variant names:

• chr9-214748-C-G
• rs549052303
• XM_047423927.1:c.-152+3432C>G

Variant summary

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

The NR_160804.1(DOCK8-AS1):​n.1003G>C 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 0.000000729 in 1,372,086 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: 7.3e-7 (0 hom.)
• Consequence: DOCK8-AS1 NR_160804.1 non_coding_transcript_exon
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.147
• 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=0.1264329).

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.1003G>C		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	NM_203447.4	MANE Select	c.-229C>G		upstream_gene	N/A	NP_982272.2	Q8NF50-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK8-AS1	ENST00000382387.4	TSL:6	n.1146G>C		non_coding_transcript_exon	Exon 1 of 1
	DOCK8-AS1	ENST00000648587.1		n.994G>C		non_coding_transcript_exon	Exon 1 of 1
	DOCK8	ENST00000432829.7	TSL:1 MANE Select	c.-229C>G		upstream_gene	N/A	ENSP00000394888.3	Q8NF50-1

Frequencies

GnomAD3 genomes Cov.: 34

GnomAD4 exome AF: 7.29e-7 AC: 1 AN: 1372086 Hom.: 0 Cov.: 85 AF XY: 0.00000148 AC XY: 1 AN XY: 676804

African (AFR) AF: 0.00 AC: 0 AN: 28290

American (AMR) AF: 0.00 AC: 0 AN: 31420

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 23554

East Asian (EAS) AF: 0.00 AC: 0 AN: 32268

South Asian (SAS) AF: 0.00 AC: 0 AN: 76388

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47822

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5572

European-Non Finnish (NFE) AF: 9.35e-7 AC: 1 AN: 1069938

Other (OTH) AF: 0.00 AC: 0 AN: 56834

GnomAD4 genome Cov.: 34

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_addAF	Benign	-0.27	T
BayesDel_noAF	Benign	-0.62
CADD	Benign	13
DANN	Benign	0.86
DEOGEN2	Benign	0.058	T
Eigen	Benign	-0.32
Eigen_PC	Benign	-0.47
FATHMM_MKL	Benign	0.22	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0092	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	0.0	N
PhyloP100		0.15
PROVEAN	Benign	0.50	N
REVEL	Benign	0.054
Sift4G	Benign	0.76	T
Polyphen		1.0	D
Vest4		0.16
MutPred		0.23		Gain of methylation at G217 (P = 0.0122)
MVP		0.099
MPC		0.65
ClinPred		0.44	T
GERP RS		2.4
PromoterAI		0.036	Neutral
Varity_R		0.10
gMVP		0.0078

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: rs549052303; hg19: chr9-214748;