10-126987579-C-G

Variant names:

• chr10-126987579-C-G
• NM_001290223.2:c.286C>G

Variant summary

Our verdict is Uncertain significance. The variant received 2 ACMG points: 2P and 0B. PM2

The NM_001290223.2(DOCK1):​c.286C>G​(p.Leu96Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DOCK1 NM_001290223.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.68
• Publications: 0 publications found

Genes affected

DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001290223.2. 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
	DOCK1	NM_001290223.2	MANE Select	c.286C>G	p.Leu96Val	missense	Exon 5 of 52	NP_001277152.2	A0A096LNH6
	DOCK1	NM_001377543.1		c.286C>G	p.Leu96Val	missense	Exon 5 of 53	NP_001364472.1
	DOCK1	NM_001377544.1		c.322C>G	p.Leu108Val	missense	Exon 6 of 53	NP_001364473.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK1	ENST00000623213.2	TSL:1 MANE Select	c.286C>G	p.Leu96Val	missense	Exon 5 of 52	ENSP00000485033.1	A0A096LNH6
	DOCK1	ENST00000280333.9	TSL:1	c.286C>G	p.Leu96Val	missense	Exon 5 of 52	ENSP00000280333.6	Q14185
	DOCK1	ENST00000939683.1		c.286C>G	p.Leu96Val	missense	Exon 5 of 52	ENSP00000609742.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.50
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.69
Eigen_PC	Uncertain	0.64
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.87	D
M_CAP	Benign	0.027	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Benign	-0.37	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		4.7
PrimateAI	Uncertain	0.73	T
PROVEAN	Benign	-2.1	N
REVEL	Uncertain	0.31
Sift	Benign	0.032	D
Sift4G	Uncertain	0.033	D
Polyphen		0.99	D
Vest4		0.84
MutPred		0.46		Gain of MoRF binding (P = 0.0927)
MVP		0.72
MPC		0.32
ClinPred		0.97	D
GERP RS		5.0
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Varity_R		0.36
gMVP		0.80
Mutation Taster		=80/20	polymorphism

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

hg19: chr10-128785843;