rs17158926

Positions:

• chr7-111870907-A-T

Variant summary

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

The NM_001363540.2(DOCK4):​c.2027+1083T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,014 control chromosomes in the GnomAD database, including 3,483 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 0.21 (3483 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.293

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=-0.83).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.2027+1083T>A		intron_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.2027+1083T>A		intron_variant		5	NM_001363540.2	ENSP00000410746	P3

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31462 AN: 151896 Hom.: 3475 Cov.: 32

Gnomad AFR AF: 0.272

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.204

Gnomad ASJ AF: 0.166

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.101

Gnomad NFE AF: 0.182

Gnomad OTH AF: 0.183

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

GnomAD4 genome AF: 0.207 AC: 31497 AN: 152014 Hom.: 3483 Cov.: 32 AF XY: 0.207 AC XY: 15354 AN XY: 74294

Gnomad4 AFR AF: 0.273

Gnomad4 AMR AF: 0.204

Gnomad4 ASJ AF: 0.166

Gnomad4 EAS AF: 0.147

Gnomad4 SAS AF: 0.138

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.182

Gnomad4 OTH AF: 0.180

Alfa AF: 0.206 Hom.: 422

Bravo AF: 0.214

Asia WGS AF: 0.115 AC: 400 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	5.6
DANN	Benign	0.81

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: rs17158926; hg19: chr7-111510963;