rs6951506

Variant names:

• chr7-111986952-G-A
• rs6951506
• NM_001363540.2:c.464+2063C>T

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 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 = 0.783 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363540.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	NM_001363540.2	MANE Select	c.464+2063C>T		intron	N/A	NP_001350469.1
	DOCK4	NM_014705.4		c.464+2063C>T		intron	N/A	NP_055520.3

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.464+2063C>T		intron	N/A	ENSP00000410746.1
	DOCK4	ENST00000437633.6	TSL:1	c.464+2063C>T		intron	N/A	ENSP00000404179.1
	DOCK4	ENST00000445943.5	TSL:5	c.425+2063C>T		intron	N/A	ENSP00000397412.1

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

African (AFR) AF: 0.791 AC: 32819 AN: 41514

American (AMR) AF: 0.300 AC: 4591 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.318 AC: 1103 AN: 3464

East Asian (EAS) AF: 0.462 AC: 2387 AN: 5168

South Asian (SAS) AF: 0.300 AC: 1447 AN: 4824

European-Finnish (FIN) AF: 0.261 AC: 2763 AN: 10570

Middle Eastern (MID) AF: 0.445 AC: 130 AN: 292

European-Non Finnish (NFE) AF: 0.294 AC: 19969 AN: 67966

Other (OTH) AF: 0.415 AC: 876 AN: 2112

Alfa AF: 0.335 Hom.: 21683

Bravo AF: 0.459

Asia WGS AF: 0.378 AC: 1318 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.33
DANN	Benign	0.48
PhyloP100		-0.63
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: rs6951506; hg19: chr7-111627007;