rs10428959

Variant names:

• chr7-112037851-C-T
• rs10428959
• NM_001363540.2:c.38-33720G>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.38-33720G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0374 in 152,128 control chromosomes in the GnomAD database, including 313 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 0.037 (313 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.278
• Publications: 4 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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.113 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.38-33720G>A		intron_variant	Intron 1 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.38-33720G>A		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.38-33720G>A		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.294-33720G>A		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.307-33720G>A		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0374 AC: 5692 AN: 152010 Hom.: 313 Cov.: 32

Gnomad AFR AF: 0.116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0223

Gnomad ASJ AF: 0.0144

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00849

Gnomad FIN AF: 0.00151

Gnomad MID AF: 0.0506

Gnomad NFE AF: 0.00540

Gnomad OTH AF: 0.0312

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

GnomAD4 genome AF: 0.0374 AC: 5686 AN: 152128 Hom.: 313 Cov.: 32 AF XY: 0.0361 AC XY: 2685 AN XY: 74386

African (AFR) AF: 0.116 AC: 4793 AN: 41486

American (AMR) AF: 0.0223 AC: 340 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.0144 AC: 50 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00829 AC: 40 AN: 4824

European-Finnish (FIN) AF: 0.00151 AC: 16 AN: 10588

Middle Eastern (MID) AF: 0.0510 AC: 15 AN: 294

European-Non Finnish (NFE) AF: 0.00540 AC: 367 AN: 67992

Other (OTH) AF: 0.0308 AC: 65 AN: 2108

Alfa AF: 0.0359 Hom.: 182

Bravo AF: 0.0430

Asia WGS AF: 0.0120 AC: 42 AN: 3464

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.0
DANN	Benign	0.57
PhyloP100		-0.28
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: rs10428959; hg19: chr7-111677906;