rs2106913

Variant names:

• chr7-112100598-G-A
• rs2106913
• NM_001363540.2:c.38-96467C>T

Your query was ambiguous. Multiple possible variants found:

• chr7-112100598-G-A
• chr7-112100598-G-T

Variant summary

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

The NM_001363540.2(DOCK4):​c.38-96467C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.186 in 152,152 control chromosomes in the GnomAD database, including 2,774 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 0.19 (2774 hom., cov: 34)
• Consequence: DOCK4 NM_001363540.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.925
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.267 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DOCK4	NM_001363540.2	c.38-96467C>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.38-96467C>T		intron_variant	Intron 1 of 52	5	NM_001363540.2	ENSP00000410746.1
DOCK4	ENST00000437633.6	c.38-96467C>T		intron_variant	Intron 1 of 51	1		ENSP00000404179.1
DOCK4	ENST00000476846.5	n.294-96467C>T		intron_variant	Intron 1 of 22	5
DOCK4	ENST00000661654.1	n.307-96467C>T		intron_variant	Intron 1 of 11

Frequencies

GnomAD3 genomes AF: 0.186 AC: 28309 AN: 152034 Hom.: 2766 Cov.: 34

Gnomad AFR AF: 0.216

Gnomad AMI AF: 0.208

Gnomad AMR AF: 0.176

Gnomad ASJ AF: 0.234

Gnomad EAS AF: 0.278

Gnomad SAS AF: 0.152

Gnomad FIN AF: 0.238

Gnomad MID AF: 0.177

Gnomad NFE AF: 0.154

Gnomad OTH AF: 0.220

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

GnomAD4 genome AF: 0.186 AC: 28332 AN: 152152 Hom.: 2774 Cov.: 34 AF XY: 0.190 AC XY: 14137 AN XY: 74364

African (AFR) AF: 0.216 AC: 8980 AN: 41518

American (AMR) AF: 0.176 AC: 2686 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.234 AC: 811 AN: 3470

East Asian (EAS) AF: 0.279 AC: 1440 AN: 5162

South Asian (SAS) AF: 0.152 AC: 734 AN: 4824

European-Finnish (FIN) AF: 0.238 AC: 2518 AN: 10558

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.154 AC: 10456 AN: 68008

Other (OTH) AF: 0.220 AC: 465 AN: 2110

Alfa AF: 0.168 Hom.: 3840

Bravo AF: 0.186

Asia WGS AF: 0.236 AC: 818 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.39
DANN	Benign	0.66
PhyloP100		-0.93
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: rs2106913; hg19: chr7-111740653;