rs10275038

Positions:

• chr7-111846970-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):​c.2601+29C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.236 in 1,608,382 control chromosomes in the GnomAD database, including 58,457 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 0.38 (16028 hom., cov: 32)
  • Exomes 𝑓: 0.22 (42429 hom.)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.342

Genes affected

DOCK4 (HGNC:19192): (dedicator of cytokinesis 4) This gene is a member of the dedicator of cytokinesis (DOCK) family and encodes a protein with a DHR-1 (CZH-1) domain, a DHR-2 (CZH-2) domain and an SH3 domain. This membrane-associated, cytoplasmic protein functions as a guanine nucleotide exchange factor and is involved in regulation of adherens junctions between cells. Mutations in this gene have been associated with ovarian, prostate, glioma, and colorectal cancers. Alternatively spliced variants which encode different protein isoforms have been described, but only one has been fully characterized. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.72).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.79 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.2601+29C>T		intron_variant		ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.2601+29C>T		intron_variant		5	NM_001363540.2	P3
DOCK4	ENST00000423057.6	c.956+29C>T		intron_variant		1
DOCK4	ENST00000437633.6	c.2601+29C>T		intron_variant		1		A1
DOCK4	ENST00000445943.5	c.2564+29C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.375 AC: 56938 AN: 151984 Hom.: 15977 Cov.: 32

Gnomad AFR AF: 0.797

Gnomad AMI AF: 0.223

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.251

Gnomad EAS AF: 0.236

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.204

Gnomad OTH AF: 0.344

GnomAD3 exomes AF: 0.248 AC: 61348 AN: 247768 Hom.: 10331 AF XY: 0.238 AC XY: 31974 AN XY: 134356

Gnomad AFR exome AF: 0.815

Gnomad AMR exome AF: 0.194

Gnomad ASJ exome AF: 0.260

Gnomad EAS exome AF: 0.237

Gnomad SAS exome AF: 0.197

Gnomad FIN exome AF: 0.220

Gnomad NFE exome AF: 0.207

Gnomad OTH exome AF: 0.227

GnomAD4 exome AF: 0.221 AC: 322080 AN: 1456280 Hom.: 42429 Cov.: 30 AF XY: 0.219 AC XY: 158478 AN XY: 724296

Gnomad4 AFR exome AF: 0.825

Gnomad4 AMR exome AF: 0.201

Gnomad4 ASJ exome AF: 0.254

Gnomad4 EAS exome AF: 0.215

Gnomad4 SAS exome AF: 0.198

Gnomad4 FIN exome AF: 0.219

Gnomad4 NFE exome AF: 0.203

Gnomad4 OTH exome AF: 0.256

GnomAD4 genome AF: 0.375 AC: 57051 AN: 152102 Hom.: 16028 Cov.: 32 AF XY: 0.368 AC XY: 27362 AN XY: 74352

Gnomad4 AFR AF: 0.797

Gnomad4 AMR AF: 0.245

Gnomad4 ASJ AF: 0.251

Gnomad4 EAS AF: 0.236

Gnomad4 SAS AF: 0.182

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.204

Gnomad4 OTH AF: 0.345

Alfa AF: 0.235 Hom.: 9444

Bravo AF: 0.399

Asia WGS AF: 0.262 AC: 911 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.72
CADD	Benign	7.8
DANN	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs10275038; hg19: chr7-111487026; COSMIC: COSV70237538;