rs1476517

chr7-111857770-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.2473+5602C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.319 in 151,932 control chromosomes in the GnomAD database, including 7,803 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 0.32 (7803 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.894

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.337 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.2473+5602C>T		intron_variant		ENST00000428084.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.2473+5602C>T		intron_variant		5	NM_001363540.2	P3
DOCK4	ENST00000423057.6	c.828+5602C>T		intron_variant		1
DOCK4	ENST00000437633.6	c.2473+5602C>T		intron_variant		1		A1
DOCK4	ENST00000445943.5	c.2436+5602C>T		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.319 AC: 48446 AN: 151814 Hom.: 7810 Cov.: 32

Gnomad AFR AF: 0.336

Gnomad AMI AF: 0.415

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.280

Gnomad EAS AF: 0.351

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.347

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.314

Gnomad OTH AF: 0.293

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

GnomAD4 genome AF: 0.319 AC: 48459 AN: 151932 Hom.: 7803 Cov.: 32 AF XY: 0.317 AC XY: 23537 AN XY: 74250

Gnomad4 AFR AF: 0.335

Gnomad4 AMR AF: 0.325

Gnomad4 ASJ AF: 0.280

Gnomad4 EAS AF: 0.350

Gnomad4 SAS AF: 0.152

Gnomad4 FIN AF: 0.347

Gnomad4 NFE AF: 0.314

Gnomad4 OTH AF: 0.290

Alfa AF: 0.306 Hom.: 7166

Bravo AF: 0.324

Asia WGS AF: 0.229 AC: 796 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
Cadd	Benign	1.4
Dann	Benign	0.95

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: rs1476517; hg19: chr7-111497826;