rs138869438

Variant names:

• chr9-420959-G-A
• NM_203447.4:c.4034G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-420959-G-A
• chr9-420959-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_203447.4(DOCK8):​c.4034G>A​(p.Ser1345Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,890 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 6.8e-7 (0 hom.)
• Consequence: DOCK8 NM_203447.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.43

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.086889565).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK8	NM_203447.4	c.4034G>A	p.Ser1345Asn	missense_variant	Exon 32 of 48	ENST00000432829.7	NP_982272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7	c.4034G>A	p.Ser1345Asn	missense_variant	Exon 32 of 48	1	NM_203447.4	ENSP00000394888.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461890 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727246

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.33	T
BayesDel_noAF	Benign	-0.71
CADD	Benign	21
DANN	Benign	0.87
DEOGEN2	Benign	0.16	T;.;.;T
Eigen	Benign	-0.66
Eigen_PC	Benign	-0.44
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Benign	0.76	T;T;T;T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.087	T;T;T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	0.90	L;.;.;.
PrimateAI	Uncertain	0.53	T
PROVEAN	Benign	-1.5	.;.;N;N
REVEL	Benign	0.12
Sift	Benign	0.35	.;.;T;T
Sift4G	Benign	0.42	T;T;T;T
Polyphen		0.0010	B;.;.;B
Vest4		0.16
MutPred		0.46		Loss of phosphorylation at S1345 (P = 0.0682);.;.;.;
MVP		0.15
MPC		0.042
ClinPred		0.083	T
GERP RS		3.8
Varity_R		0.065
gMVP		0.25

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-420959; COSMIC: COSV66621286;