rs2074114

Positions:

• chr7-111811603-T-C
• chr7-111811603-T-G

Variant summary

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

The NM_001363540.2(DOCK4):​c.3006+271A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 151,974 control chromosomes in the GnomAD database, including 18,192 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 0.41 (18192 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.31

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]

DOCK4-AS1 (HGNC:40876): (DOCK4 antisense RNA 1)

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.818 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DOCK4	NM_001363540.2	c.3006+271A>G		intron_variant		ENST00000428084.6
DOCK4-AS1	NR_103806.1	n.109+2990T>C		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DOCK4	ENST00000428084.6	c.3006+271A>G		intron_variant		5	NM_001363540.2	P3
DOCK4-AS1	ENST00000452714.1	n.98+2990T>C		intron_variant, non_coding_transcript_variant		1

Frequencies

GnomAD3 genomes AF: 0.407 AC: 61827 AN: 151856 Hom.: 18139 Cov.: 32

Gnomad AFR AF: 0.825

Gnomad AMI AF: 0.226

Gnomad AMR AF: 0.350

Gnomad ASJ AF: 0.176

Gnomad EAS AF: 0.581

Gnomad SAS AF: 0.138

Gnomad FIN AF: 0.274

Gnomad MID AF: 0.272

Gnomad NFE AF: 0.208

Gnomad OTH AF: 0.369

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

GnomAD4 genome AF: 0.408 AC: 61943 AN: 151974 Hom.: 18192 Cov.: 32 AF XY: 0.406 AC XY: 30188 AN XY: 74278

Gnomad4 AFR AF: 0.825

Gnomad4 AMR AF: 0.350

Gnomad4 ASJ AF: 0.176

Gnomad4 EAS AF: 0.581

Gnomad4 SAS AF: 0.139

Gnomad4 FIN AF: 0.274

Gnomad4 NFE AF: 0.208

Gnomad4 OTH AF: 0.368

Alfa AF: 0.239 Hom.: 7169

Bravo AF: 0.439

Asia WGS AF: 0.359 AC: 1245 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	1.6
DANN	Benign	0.33

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: rs2074114; hg19: chr7-111451659;