rs2379118

Positions:

• chrX-118685810-A-C

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK11	NM_144658.4	c.*3A>C		3_prime_UTR_variant	53/53	ENST00000276202.9	NP_653259.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK11	ENST00000276202.9	c.*3A>C		3_prime_UTR_variant	53/53	1	NM_144658.4	ENSP00000276202.7
DOCK11	ENST00000276204.10	c.*3A>C		3_prime_UTR_variant	53/53	5		ENSP00000276204.6
DOCK11	ENST00000633080.1	c.*3A>C		3_prime_UTR_variant	49/49	5		ENSP00000487829.1
DOCK11	ENST00000632573.1	c.*135A>C		3_prime_UTR_variant	3/3	2		ENSP00000488503.1

Frequencies

GnomAD3 genomes AF: 0.147 AC: 16476 AN: 111740 Hom.: 1000 Cov.: 24 AF XY: 0.151 AC XY: 5112 AN XY: 33918

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

GnomAD3 exomes AF: 0.184 AC: 33330 AN: 181365 Hom.: 2069 AF XY: 0.188 AC XY: 12371 AN XY: 65909

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 SAS exome AF: 0.238

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

Gnomad4 AFR exome AF: 0.0600

Gnomad4 AMR exome AF: 0.267

Gnomad4 ASJ exome AF: 0.151

Gnomad4 EAS exome AF: 0.187

Gnomad4 SAS exome AF: 0.238

Gnomad4 FIN exome AF: 0.176

Gnomad4 NFE exome AF: 0.170

Gnomad4 OTH exome AF: 0.172

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

Gnomad4 AFR AF: 0.0610

Gnomad4 AMR AF: 0.259

Gnomad4 ASJ AF: 0.159

Gnomad4 EAS AF: 0.199

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.166

Gnomad4 NFE AF: 0.166

Gnomad4 OTH AF: 0.173

Alfa AF: 0.163 Hom.: 6088

Bravo AF: 0.153

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	13
DANN	Benign	0.82
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

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

Publications

LitVar

Other links and lift over

dbSNP: rs2379118; hg19: chrX-117819773; COSMIC: COSV52235635;