rs2379118

Variant names:

• chrX-118685810-A-C
• rs2379118
• NM_144658.4:c.*3A>C

Variant summary

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

The NM_144658.4(DOCK11):​c.*3A>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.172 in 1,208,689 control chromosomes in the GnomAD database, including 12,289 homozygotes. There are 69,409 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 0.15 (999 hom., 5123 hem., cov: 24)
  • Exomes 𝑓: 0.17 (11290 hom. 64286 hem.)
• Consequence: DOCK11 NM_144658.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.39
• Publications: 8 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=-0.47).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.251 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.*3A>C		3_prime_UTR	Exon 53 of 53	NP_653259.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK11	ENST00000276202.9	TSL:1 MANE Select	c.*3A>C		3_prime_UTR	Exon 53 of 53	ENSP00000276202.7
	DOCK11	ENST00000276204.10	TSL:5	c.*3A>C		3_prime_UTR	Exon 53 of 53	ENSP00000276204.6
	DOCK11	ENST00000633080.1	TSL:5	c.*3A>C		3_prime_UTR	Exon 49 of 49	ENSP00000487829.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16476 AN: 111740 Hom.: 1000 Cov.: 24

Gnomad AFR AF: 0.0610

Gnomad AMI AF: 0.0705

Gnomad AMR AF: 0.259

Gnomad ASJ AF: 0.159

Gnomad EAS AF: 0.198

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.166

Gnomad MID AF: 0.218

Gnomad NFE AF: 0.166

Gnomad OTH AF: 0.172

GnomAD2 exomes AF: 0.184 AC: 33330 AN: 181365 AF XY: 0.188

Gnomad AFR exome AF: 0.0570

Gnomad AMR exome AF: 0.268

Gnomad ASJ exome AF: 0.157

Gnomad EAS exome AF: 0.207

Gnomad FIN exome AF: 0.173

Gnomad NFE exome AF: 0.164

Gnomad OTH exome AF: 0.190

GnomAD4 exome AF: 0.174 AC: 191021 AN: 1096894 Hom.: 11290 Cov.: 30 AF XY: 0.177 AC XY: 64286 AN XY: 362390

African (AFR) AF: 0.0600 AC: 1582 AN: 26381

American (AMR) AF: 0.267 AC: 9360 AN: 35092

Ashkenazi Jewish (ASJ) AF: 0.151 AC: 2917 AN: 19343

East Asian (EAS) AF: 0.187 AC: 5645 AN: 30161

South Asian (SAS) AF: 0.238 AC: 12847 AN: 53876

European-Finnish (FIN) AF: 0.176 AC: 7144 AN: 40487

Middle Eastern (MID) AF: 0.200 AC: 826 AN: 4126

European-Non Finnish (NFE) AF: 0.170 AC: 142760 AN: 841375

Other (OTH) AF: 0.172 AC: 7940 AN: 46053

GnomAD4 genome AF: 0.147 AC: 16483 AN: 111795 Hom.: 999 Cov.: 24 AF XY: 0.151 AC XY: 5123 AN XY: 33983

African (AFR) AF: 0.0610 AC: 1887 AN: 30919

American (AMR) AF: 0.259 AC: 2709 AN: 10466

Ashkenazi Jewish (ASJ) AF: 0.159 AC: 420 AN: 2636

East Asian (EAS) AF: 0.199 AC: 709 AN: 3569

South Asian (SAS) AF: 0.217 AC: 594 AN: 2733

European-Finnish (FIN) AF: 0.166 AC: 987 AN: 5953

Middle Eastern (MID) AF: 0.226 AC: 49 AN: 217

European-Non Finnish (NFE) AF: 0.166 AC: 8817 AN: 53103

Other (OTH) AF: 0.173 AC: 263 AN: 1518

Alfa AF: 0.162 Hom.: 7777

Bravo AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		2.4
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1
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: rs2379118; hg19: chrX-117819773; COSMIC: COSV52235635;