7-111887504-G-A

Variant names:

• chr7-111887504-G-A
• rs10255299
• NM_001363540.2:c.1587+8108C>T

Variant summary

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

The NM_001363540.2(DOCK4):​c.1587+8108C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 152,100 control chromosomes in the GnomAD database, including 1,063 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 0.11 (1063 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.00500
• Publications: 8 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.184 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.1587+8108C>T		intron_variant	Intron 16 of 52	ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.1587+8108C>T		intron_variant	Intron 16 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.1587+8108C>T		intron_variant	Intron 16 of 51	1		ENSP00000404179.1
DOCK4	ENST00000445943.5	c.1548+8108C>T		intron_variant	Intron 15 of 52	5		ENSP00000397412.1
DOCK4	ENST00000476846.5	n.1843+8108C>T		intron_variant	Intron 16 of 22	5

Frequencies

GnomAD3 genomes AF: 0.106 AC: 16117 AN: 151982 Hom.: 1054 Cov.: 32

Gnomad AFR AF: 0.187

Gnomad AMI AF: 0.0746

Gnomad AMR AF: 0.0594

Gnomad ASJ AF: 0.133

Gnomad EAS AF: 0.00695

Gnomad SAS AF: 0.126

Gnomad FIN AF: 0.0742

Gnomad MID AF: 0.114

Gnomad NFE AF: 0.0774

Gnomad OTH AF: 0.110

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

GnomAD4 genome AF: 0.106 AC: 16165 AN: 152100 Hom.: 1063 Cov.: 32 AF XY: 0.105 AC XY: 7822 AN XY: 74366

African (AFR) AF: 0.188 AC: 7779 AN: 41462

American (AMR) AF: 0.0592 AC: 905 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.133 AC: 460 AN: 3468

East Asian (EAS) AF: 0.00697 AC: 36 AN: 5168

South Asian (SAS) AF: 0.125 AC: 603 AN: 4818

European-Finnish (FIN) AF: 0.0742 AC: 785 AN: 10586

Middle Eastern (MID) AF: 0.116 AC: 34 AN: 294

European-Non Finnish (NFE) AF: 0.0774 AC: 5260 AN: 68000

Other (OTH) AF: 0.111 AC: 235 AN: 2112

Alfa AF: 0.0851 Hom.: 2785

Bravo AF: 0.107

Asia WGS AF: 0.0790 AC: 274 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		-0.0050
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: rs10255299; hg19: chr7-111527560;