rs6951506

Positions:

• chr7-111986952-G-A
• chr7-111986952-G-C

Variant summary

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

The NM_001363540.2(DOCK4):​c.464+2063C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.438 in 152,104 control chromosomes in the GnomAD database, including 18,411 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 0.44 (18411 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.629

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.783 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.464+2063C>T		intron_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.464+2063C>T		intron_variant		5	NM_001363540.2	ENSP00000410746	P3

Frequencies

GnomAD3 genomes AF: 0.437 AC: 66468 AN: 151986 Hom.: 18357 Cov.: 32

Gnomad AFR AF: 0.790

Gnomad AMI AF: 0.535

Gnomad AMR AF: 0.301

Gnomad ASJ AF: 0.318

Gnomad EAS AF: 0.462

Gnomad SAS AF: 0.300

Gnomad FIN AF: 0.261

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.294

Gnomad OTH AF: 0.417

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

GnomAD4 genome AF: 0.438 AC: 66572 AN: 152104 Hom.: 18411 Cov.: 32 AF XY: 0.429 AC XY: 31925 AN XY: 74350

Gnomad4 AFR AF: 0.791

Gnomad4 AMR AF: 0.300

Gnomad4 ASJ AF: 0.318

Gnomad4 EAS AF: 0.462

Gnomad4 SAS AF: 0.300

Gnomad4 FIN AF: 0.261

Gnomad4 NFE AF: 0.294

Gnomad4 OTH AF: 0.415

Alfa AF: 0.321 Hom.: 13075

Bravo AF: 0.459

Asia WGS AF: 0.378 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.48

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: rs6951506; hg19: chr7-111627007;