rs2560643

Variant names:

• chr7-112148286-T-A
• rs2560643
• NM_001363540.2:c.37+57816A>T

Your query was ambiguous. Multiple possible variants found:

• chr7-112148286-T-A
• chr7-112148286-T-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.37+57816A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.499 in 151,894 control chromosomes in the GnomAD database, including 19,080 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 0.50 (19080 hom., cov: 31)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.138
• Publications: 1 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 (SAS) allele frequency at 95% confidence interval = 0.634 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.37+57816A>T		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.37+57816A>T		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.37+57816A>T		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.293+57816A>T		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.306+57816A>T		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.499 AC: 75771 AN: 151776 Hom.: 19066 Cov.: 31

Gnomad AFR AF: 0.497

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.435

Gnomad ASJ AF: 0.495

Gnomad EAS AF: 0.572

Gnomad SAS AF: 0.655

Gnomad FIN AF: 0.545

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.492

Gnomad OTH AF: 0.489

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

GnomAD4 genome AF: 0.499 AC: 75820 AN: 151894 Hom.: 19080 Cov.: 31 AF XY: 0.504 AC XY: 37407 AN XY: 74234

African (AFR) AF: 0.497 AC: 20578 AN: 41412

American (AMR) AF: 0.435 AC: 6637 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.495 AC: 1718 AN: 3470

East Asian (EAS) AF: 0.572 AC: 2939 AN: 5136

South Asian (SAS) AF: 0.653 AC: 3145 AN: 4814

European-Finnish (FIN) AF: 0.545 AC: 5753 AN: 10548

Middle Eastern (MID) AF: 0.438 AC: 128 AN: 292

European-Non Finnish (NFE) AF: 0.492 AC: 33430 AN: 67954

Other (OTH) AF: 0.492 AC: 1035 AN: 2102

Alfa AF: 0.494 Hom.: 2293

Bravo AF: 0.486

Asia WGS AF: 0.607 AC: 2111 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	3.1
DANN	Benign	0.67
PhyloP100		0.14
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: rs2560643; hg19: chr7-111788341;