7-111725879-C-G

Variant names:

• chr7-111725879-C-G
• rs1859746
• NM_001363540.2:c.*2395G>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.*2395G>C variant causes a downstream gene change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.393 in 151,954 control chromosomes in the GnomAD database, including 12,202 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 0.39 (12202 hom., cov: 33)
• Consequence: DOCK4 NM_001363540.2 downstream_gene
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.302
• 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=-0.85).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.612 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.*2395G>C		downstream_gene_variant		ENST00000428084.6	NP_001350469.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DOCK4	ENST00000428084.6	c.*2395G>C		downstream_gene_variant		5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.*2395G>C		downstream_gene_variant		1		ENSP00000404179.1
DOCK4	ENST00000423057.6	c.*2395G>C		downstream_gene_variant		1		ENSP00000412834.1

Frequencies

GnomAD3 genomes AF: 0.392 AC: 59586 AN: 151836 Hom.: 12173 Cov.: 33

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.291

Gnomad AMR AF: 0.498

Gnomad ASJ AF: 0.456

Gnomad EAS AF: 0.414

Gnomad SAS AF: 0.631

Gnomad FIN AF: 0.370

Gnomad MID AF: 0.551

Gnomad NFE AF: 0.354

Gnomad OTH AF: 0.411

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

GnomAD4 genome AF: 0.393 AC: 59661 AN: 151954 Hom.: 12202 Cov.: 33 AF XY: 0.399 AC XY: 29647 AN XY: 74282

African (AFR) AF: 0.387 AC: 16044 AN: 41440

American (AMR) AF: 0.498 AC: 7610 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.456 AC: 1583 AN: 3468

East Asian (EAS) AF: 0.413 AC: 2132 AN: 5158

South Asian (SAS) AF: 0.631 AC: 3040 AN: 4820

European-Finnish (FIN) AF: 0.370 AC: 3895 AN: 10540

Middle Eastern (MID) AF: 0.562 AC: 164 AN: 292

European-Non Finnish (NFE) AF: 0.354 AC: 24053 AN: 67938

Other (OTH) AF: 0.414 AC: 875 AN: 2112

Alfa AF: 0.200 Hom.: 386

Bravo AF: 0.397

Asia WGS AF: 0.570 AC: 1982 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.66
DANN	Benign	0.68
PhyloP100		-0.30

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1859746; hg19: chr7-111365935;