19-11228985-TAC-AAG

Variant names:

• chr19-11228985-TAC-AAG
• NM_020812.4:c.2767_2769delGTAinsCTT
• DOCK6 p.Val923Leu

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_020812.4(DOCK6):​c.2767_2769delGTAinsCTT​(p.Val923Leu) variant causes a missense change involving the alteration of a conserved nucleotide. 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. V923I) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DOCK6 NM_020812.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.75
• Publications: 0 publications found

Genes affected

DOCK6 (HGNC:19189): (dedicator of cytokinesis 6) This gene encodes a member of the dedicator of cytokinesis (DOCK) family of atypical guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with small GTPases and are components of intracellular signaling networks. The encoded protein is a group C DOCK protein and plays a role in actin cytoskeletal reorganization by activating the Rho GTPases Cdc42 and Rac1. Mutations in this gene are associated with Adams-Oliver syndrome 2. [provided by RefSeq, Dec 2011]

DOCK6 Gene-Disease associations (from GenCC):

• Adams-Oliver syndrome

  Inheritance: AR, AD Classification: DEFINITIVE, SUPPORTIVE Submitted by: ClinGen, Orphanet
• Adams-Oliver syndrome 2

  Inheritance: AR Classification: STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: No computational evidence supports a deleterious effect, but strongly conserved according to phyloP

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020812.4. 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
	DOCK6	NM_020812.4	MANE Select	c.2767_2769delGTAinsCTT	p.Val923Leu	missense	N/A	NP_065863.2	Q96HP0
	DOCK6	NM_001367830.1		c.2872_2874delGTAinsCTT	p.Val958Leu	missense	N/A	NP_001354759.1	K7ESB7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK6	ENST00000294618.12	TSL:1 MANE Select	c.2767_2769delGTAinsCTT	p.Val923Leu	missense	N/A	ENSP00000294618.6	Q96HP0
	DOCK6	ENST00000587656.6	TSL:5	c.2872_2874delGTAinsCTT	p.Val958Leu	missense	N/A	ENSP00000468638.2	K7ESB7
	DOCK6	ENST00000590680.5	TSL:5	c.1201_1203delGTAinsCTT	p.Val401Leu	missense	N/A	ENSP00000467191.1	K7EP20

Frequencies

GnomAD3 genomes Cov.: 31

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

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		7.7

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: chr19-11339661;