rs29465

Variant names:

• chr7-111989969-C-T
• rs29465
• NM_001363540.2:c.316-806G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):​c.316-806G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.449 in 151,546 control chromosomes in the GnomAD database, including 15,564 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 0.45 (15564 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.11
• Publications: 2 publications found

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

Our verdict: Benign. The variant received -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 = 0.505 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.316-806G>A		intron_variant	Intron 5 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.316-806G>A		intron_variant	Intron 5 of 52	5	NM_001363540.2	ENSP00000410746.1

Frequencies

GnomAD3 genomes AF: 0.449 AC: 68028 AN: 151428 Hom.: 15541 Cov.: 32

Gnomad AFR AF: 0.511

Gnomad AMI AF: 0.290

Gnomad AMR AF: 0.443

Gnomad ASJ AF: 0.361

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.307

Gnomad FIN AF: 0.547

Gnomad MID AF: 0.248

Gnomad NFE AF: 0.417

Gnomad OTH AF: 0.408

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

GnomAD4 genome AF: 0.449 AC: 68090 AN: 151546 Hom.: 15564 Cov.: 32 AF XY: 0.453 AC XY: 33532 AN XY: 74048

African (AFR) AF: 0.510 AC: 21051 AN: 41242

American (AMR) AF: 0.444 AC: 6770 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.361 AC: 1252 AN: 3470

East Asian (EAS) AF: 0.456 AC: 2348 AN: 5144

South Asian (SAS) AF: 0.308 AC: 1485 AN: 4816

European-Finnish (FIN) AF: 0.547 AC: 5719 AN: 10464

Middle Eastern (MID) AF: 0.252 AC: 74 AN: 294

European-Non Finnish (NFE) AF: 0.417 AC: 28265 AN: 67840

Other (OTH) AF: 0.409 AC: 863 AN: 2110

Alfa AF: 0.418 Hom.: 56716

Bravo AF: 0.446

Asia WGS AF: 0.403 AC: 1398 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	0.37
DANN	Benign	0.20
PhyloP100		-1.1
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs29465; hg19: chr7-111630024;