rs2890080

Variant names:

• chrX-118684873-C-A
• rs2890080
• NM_144658.4:c.6103-815C>A

Your query was ambiguous. Multiple possible variants found:

• chrX-118684873-C-A
• chrX-118684873-C-T

Variant summary

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

The NM_144658.4(DOCK11):​c.6103-815C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.111 in 111,381 control chromosomes in the GnomAD database, including 1,016 homozygotes. There are 3,309 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 0.11 (1016 hom., 3309 hem., cov: 22)
• Consequence: DOCK11 NM_144658.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0600
• Publications: 0 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=-0.73).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.272 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_144658.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK11	NM_144658.4	MANE Select	c.6103-815C>A		intron	N/A	NP_653259.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK11	ENST00000276202.9	TSL:1 MANE Select	c.6103-815C>A		intron	N/A	ENSP00000276202.7
	DOCK11	ENST00000276204.10	TSL:5	c.6115-815C>A		intron	N/A	ENSP00000276204.6
	DOCK11	ENST00000633080.1	TSL:5	c.5590-815C>A		intron	N/A	ENSP00000487829.1

Frequencies

GnomAD3 genomes AF: 0.111 AC: 12334 AN: 111327 Hom.: 1016 Cov.: 22

Gnomad AFR AF: 0.277

Gnomad AMI AF: 0.0337

Gnomad AMR AF: 0.0517

Gnomad ASJ AF: 0.0558

Gnomad EAS AF: 0.000560

Gnomad SAS AF: 0.0192

Gnomad FIN AF: 0.0605

Gnomad MID AF: 0.0596

Gnomad NFE AF: 0.0493

Gnomad OTH AF: 0.0883

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

GnomAD4 genome AF: 0.111 AC: 12345 AN: 111381 Hom.: 1016 Cov.: 22 AF XY: 0.0984 AC XY: 3309 AN XY: 33637

African (AFR) AF: 0.277 AC: 8463 AN: 30574

American (AMR) AF: 0.0516 AC: 541 AN: 10476

Ashkenazi Jewish (ASJ) AF: 0.0558 AC: 148 AN: 2652

East Asian (EAS) AF: 0.000561 AC: 2 AN: 3563

South Asian (SAS) AF: 0.0185 AC: 50 AN: 2697

European-Finnish (FIN) AF: 0.0605 AC: 358 AN: 5914

Middle Eastern (MID) AF: 0.0512 AC: 11 AN: 215

European-Non Finnish (NFE) AF: 0.0493 AC: 2619 AN: 53106

Other (OTH) AF: 0.0866 AC: 130 AN: 1502

Alfa AF: 0.143 Hom.: 2406

Bravo AF: 0.120

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.73
CADD	Benign	9.0
DANN	Benign	0.81
PhyloP100		0.060
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: rs2890080; hg19: chrX-117818836;