rs2074127

Positions:

• chr7-111984467-T-C

Variant summary

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

The NM_001363540.2(DOCK4):​c.465-77A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.214 in 1,268,878 control chromosomes in the GnomAD database, including 33,541 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 0.28 (7342 hom., cov: 32)
  • Exomes 𝑓: 0.20 (26199 hom.)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.26

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]

DOCK4 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.484 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.465-77A>G		intron_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.465-77A>G		intron_variant		5	NM_001363540.2	ENSP00000410746.1

Frequencies

GnomAD3 genomes AF: 0.281 AC: 42762 AN: 151984 Hom.: 7318 Cov.: 32

Gnomad AFR AF: 0.489

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.202

Gnomad ASJ AF: 0.232

Gnomad EAS AF: 0.374

Gnomad SAS AF: 0.217

Gnomad FIN AF: 0.191

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.187

Gnomad OTH AF: 0.262

GnomAD4 exome AF: 0.204 AC: 228326 AN: 1116776 Hom.: 26199 AF XY: 0.204 AC XY: 114523 AN XY: 562598

Gnomad4 AFR exome AF: 0.504

Gnomad4 AMR exome AF: 0.175

Gnomad4 ASJ exome AF: 0.226

Gnomad4 EAS exome AF: 0.350

Gnomad4 SAS exome AF: 0.214

Gnomad4 FIN exome AF: 0.191

Gnomad4 NFE exome AF: 0.188

Gnomad4 OTH exome AF: 0.228

GnomAD4 genome AF: 0.282 AC: 42822 AN: 152102 Hom.: 7342 Cov.: 32 AF XY: 0.279 AC XY: 20734 AN XY: 74346

Gnomad4 AFR AF: 0.490

Gnomad4 AMR AF: 0.201

Gnomad4 ASJ AF: 0.232

Gnomad4 EAS AF: 0.374

Gnomad4 SAS AF: 0.216

Gnomad4 FIN AF: 0.191

Gnomad4 NFE AF: 0.187

Gnomad4 OTH AF: 0.261

Alfa AF: 0.226 Hom.: 705

Bravo AF: 0.296

Asia WGS AF: 0.288 AC: 1005 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.0050
DANN	Benign	0.51

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: rs2074127; hg19: chr7-111624522;