rs955220

Variant names:

• chr9-436779-T-C
• rs955220
• NM_203447.4:c.5079+1804T>C

Your query was ambiguous. Multiple possible variants found:

• chr9-436779-T-C
• chr9-436779-T-G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_203447.4(DOCK8):​c.5079+1804T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.409 in 152,206 control chromosomes in the GnomAD database, including 15,274 homozygotes. 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: 𝑓 0.41 (15274 hom., cov: 33)
• Consequence: DOCK8 NM_203447.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.938
• Publications: 4 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 Gene-Disease associations (from GenCC):

• combined immunodeficiency due to DOCK8 deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• complex neurodevelopmental disorder

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.83).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.552 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK8	NM_203447.4	c.5079+1804T>C		intron_variant	Intron 39 of 47	ENST00000432829.7	NP_982272.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK8	ENST00000432829.7	c.5079+1804T>C		intron_variant	Intron 39 of 47	1	NM_203447.4	ENSP00000394888.3

Frequencies

GnomAD3 genomes AF: 0.410 AC: 62312 AN: 152088 Hom.: 15274 Cov.: 33

Gnomad AFR AF: 0.127

Gnomad AMI AF: 0.575

Gnomad AMR AF: 0.414

Gnomad ASJ AF: 0.418

Gnomad EAS AF: 0.549

Gnomad SAS AF: 0.388

Gnomad FIN AF: 0.482

Gnomad MID AF: 0.525

Gnomad NFE AF: 0.557

Gnomad OTH AF: 0.428

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.409 AC: 62313 AN: 152206 Hom.: 15274 Cov.: 33 AF XY: 0.406 AC XY: 30215 AN XY: 74396

African (AFR) AF: 0.127 AC: 5268 AN: 41556

American (AMR) AF: 0.414 AC: 6333 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.418 AC: 1452 AN: 3470

East Asian (EAS) AF: 0.549 AC: 2844 AN: 5180

South Asian (SAS) AF: 0.390 AC: 1880 AN: 4826

European-Finnish (FIN) AF: 0.482 AC: 5097 AN: 10574

Middle Eastern (MID) AF: 0.520 AC: 153 AN: 294

European-Non Finnish (NFE) AF: 0.557 AC: 37858 AN: 67988

Other (OTH) AF: 0.427 AC: 904 AN: 2116

Alfa AF: 0.354 Hom.: 1146

Bravo AF: 0.394

Asia WGS AF: 0.406 AC: 1411 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	13
DANN	Benign	0.55
PhyloP100		0.94
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: rs955220; hg19: chr9-436779;