7-111811913-TG-CA

Variant names:

• chr7-111811913-TG-CA
• NM_001363540.2:c.2966_2967delCAinsTG
• DOCK4 p.Ala989Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001363540.2(DOCK4):​c.2966_2967delCAinsTG​(p.Ala989Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A989G) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOCK4 NM_001363540.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.20
• 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]

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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001363540.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	NM_001363540.2	MANE Select	c.2966_2967delCAinsTG	p.Ala989Val	missense	N/A	NP_001350469.1	Q8N1I0-3
	DOCK4	NM_014705.4		c.2966_2967delCAinsTG	p.Ala989Val	missense	N/A	NP_055520.3
	DOCK4-AS1	NR_103806.1		n.109+3300_109+3301delTGinsCA		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK4	ENST00000428084.6	TSL:5 MANE Select	c.2966_2967delCAinsTG	p.Ala989Val	missense	N/A	ENSP00000410746.1	Q8N1I0-3
	DOCK4	ENST00000437633.6	TSL:1	c.2966_2967delCAinsTG	p.Ala989Val	missense	N/A	ENSP00000404179.1	Q8N1I0-1
	DOCK4	ENST00000423057.6	TSL:1	c.1319_1320delCAinsTG	p.Ala440Val	missense	N/A	ENSP00000412834.1	H0Y7H7

Frequencies

GnomAD3 genomes Cov.: 32

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

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr7-111451969;