rs17326758

Variant names:

• chrX-118641602-T-G
• rs17326758
• NM_144658.4:c.4260+297T>G

Variant summary

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

The NM_144658.4(DOCK11):​c.4260+297T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.098 in 111,183 control chromosomes in the GnomAD database, including 477 homozygotes. There are 3,308 hemizygotes in GnomAD. 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 0.098 (477 hom., 3308 hem., cov: 22)
• Consequence: DOCK11 NM_144658.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0550
• Publications: 1 publications found

Genes affected

DOCK11 (HGNC:23483): (dedicator of cytokinesis 11) Predicted to enable guanyl-nucleotide exchange factor activity. Predicted to be involved in several processes, including marginal zone B cell differentiation; positive regulation of GTPase activity; and positive regulation of filopodium assembly. Predicted to be located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

DOCK11 Gene-Disease associations (from GenCC):

• autoinflammatory disease, multisystem, with immune dysregulation, X-linked

  Inheritance: XL 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=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.135 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK11	NM_144658.4	c.4260+297T>G		intron_variant	Intron 39 of 52	ENST00000276202.9	NP_653259.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK11	ENST00000276202.9	c.4260+297T>G		intron_variant	Intron 39 of 52	1	NM_144658.4	ENSP00000276202.7
DOCK11	ENST00000276204.10	c.4260+297T>G		intron_variant	Intron 39 of 52	5		ENSP00000276204.6
DOCK11	ENST00000633080.1	c.3747+297T>G		intron_variant	Intron 35 of 48	5		ENSP00000487829.1

Frequencies

GnomAD3 genomes AF: 0.0981 AC: 10900 AN: 111127 Hom.: 478 Cov.: 22

Gnomad AFR AF: 0.0230

Gnomad AMI AF: 0.122

Gnomad AMR AF: 0.108

Gnomad ASJ AF: 0.0794

Gnomad EAS AF: 0.106

Gnomad SAS AF: 0.147

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.132

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.0980 AC: 10901 AN: 111183 Hom.: 477 Cov.: 22 AF XY: 0.0991 AC XY: 3308 AN XY: 33377

African (AFR) AF: 0.0230 AC: 708 AN: 30717

American (AMR) AF: 0.108 AC: 1124 AN: 10381

Ashkenazi Jewish (ASJ) AF: 0.0794 AC: 210 AN: 2644

East Asian (EAS) AF: 0.106 AC: 377 AN: 3552

South Asian (SAS) AF: 0.147 AC: 389 AN: 2645

European-Finnish (FIN) AF: 0.152 AC: 894 AN: 5863

Middle Eastern (MID) AF: 0.126 AC: 27 AN: 215

European-Non Finnish (NFE) AF: 0.131 AC: 6921 AN: 52972

Other (OTH) AF: 0.111 AC: 168 AN: 1513

Alfa AF: 0.116 Hom.: 3280

Bravo AF: 0.0934

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	1.1
DANN	Benign	0.75
PhyloP100		-0.055
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: rs17326758; hg19: chrX-117775565;