chr7-112005137-A-C

Variant names:

• chr7-112005137-A-C
• rs10487337
• NM_001363540.2:c.38-1006T>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001363540.2(DOCK4):​c.38-1006T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0584 in 152,288 control chromosomes in the GnomAD database, including 394 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 0.058 (394 hom., cov: 32)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.60
• 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=-0.76).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.169 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.38-1006T>G		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.38-1006T>G		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.38-1006T>G		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.294-1006T>G		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.307-1006T>G		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.0582 AC: 8858 AN: 152170 Hom.: 379 Cov.: 32

Gnomad AFR AF: 0.103

Gnomad AMI AF: 0.00219

Gnomad AMR AF: 0.0733

Gnomad ASJ AF: 0.0193

Gnomad EAS AF: 0.178

Gnomad SAS AF: 0.0872

Gnomad FIN AF: 0.00933

Gnomad MID AF: 0.00955

Gnomad NFE AF: 0.0269

Gnomad OTH AF: 0.0541

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

GnomAD4 genome AF: 0.0584 AC: 8899 AN: 152288 Hom.: 394 Cov.: 32 AF XY: 0.0591 AC XY: 4401 AN XY: 74464

African (AFR) AF: 0.104 AC: 4324 AN: 41560

American (AMR) AF: 0.0732 AC: 1119 AN: 15292

Ashkenazi Jewish (ASJ) AF: 0.0193 AC: 67 AN: 3472

East Asian (EAS) AF: 0.178 AC: 923 AN: 5184

South Asian (SAS) AF: 0.0871 AC: 420 AN: 4824

European-Finnish (FIN) AF: 0.00933 AC: 99 AN: 10614

Middle Eastern (MID) AF: 0.0137 AC: 4 AN: 292

European-Non Finnish (NFE) AF: 0.0269 AC: 1829 AN: 68026

Other (OTH) AF: 0.0530 AC: 112 AN: 2112

Alfa AF: 0.0339 Hom.: 136

Bravo AF: 0.0642

Asia WGS AF: 0.116 AC: 405 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.76
CADD	Benign	10
DANN	Benign	0.86
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: rs10487337; hg19: chr7-111645192;