rs6977379

Variant names:

• chr7-112181775-T-G
• rs6977379
• NM_001363540.2:c.37+24327A>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+24327A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0689 in 152,116 control chromosomes in the GnomAD database, including 803 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 0.069 (803 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.56
• Publications: 0 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=-0.82).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.178 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.37+24327A>C		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+24327A>C		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.37+24327A>C		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.293+24327A>C		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.306+24327A>C		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0687 AC: 10436 AN: 151998 Hom.: 795 Cov.: 32

Gnomad AFR AF: 0.181

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0963

Gnomad ASJ AF: 0.0320

Gnomad EAS AF: 0.00116

Gnomad SAS AF: 0.0309

Gnomad FIN AF: 0.00813

Gnomad MID AF: 0.0316

Gnomad NFE AF: 0.0151

Gnomad OTH AF: 0.0489

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

GnomAD4 genome AF: 0.0689 AC: 10483 AN: 152116 Hom.: 803 Cov.: 32 AF XY: 0.0682 AC XY: 5067 AN XY: 74346

African (AFR) AF: 0.181 AC: 7515 AN: 41470

American (AMR) AF: 0.0968 AC: 1480 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.0320 AC: 111 AN: 3470

East Asian (EAS) AF: 0.00116 AC: 6 AN: 5180

South Asian (SAS) AF: 0.0309 AC: 149 AN: 4820

European-Finnish (FIN) AF: 0.00813 AC: 86 AN: 10572

Middle Eastern (MID) AF: 0.0340 AC: 10 AN: 294

European-Non Finnish (NFE) AF: 0.0151 AC: 1024 AN: 68004

Other (OTH) AF: 0.0483 AC: 102 AN: 2110

Alfa AF: 0.0243 Hom.: 180

Bravo AF: 0.0803

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	8.5
DANN	Benign	0.52
PhyloP100		2.6
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: rs6977379; hg19: chr7-111821830;