10-127447420-G-C

Position:

• chr10-127447420-G-C

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001290223.2(DOCK1):​c.5440G>C​(p.Ala1814Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 33)
• Consequence: DOCK1 NM_001290223.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.848

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

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.0411911).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DOCK1	NM_001290223.2	c.5440G>C	p.Ala1814Pro	missense_variant	51/52	ENST00000623213.2	NP_001277152.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DOCK1	ENST00000623213.2	c.5440G>C	p.Ala1814Pro	missense_variant	51/52	1	NM_001290223.2	ENSP00000485033.1
DOCK1	ENST00000280333.9	c.5377G>C	p.Ala1793Pro	missense_variant	51/52	1		ENSP00000280333.6

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.38	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.33
DANN	Benign	0.88
DEOGEN2	Benign	0.090	T;T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.6
FATHMM_MKL	Benign	0.036	N
LIST_S2	Benign	0.53	T;T
M_CAP	Benign	0.010	T
MetaRNN	Benign	0.041	T;T
MetaSVM	Benign	-0.92	T
MutationAssessor	Benign	-0.14	N;.
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.47	N;.
REVEL	Benign	0.098
Sift	Benign	0.30	T;.
Sift4G	Benign	0.30	T;T
Polyphen		0.0	B;.
Vest4		0.075
MutPred		0.20		Loss of catalytic residue at A1793 (P = 0.0578);.;
MVP		0.40
MPC		0.31
ClinPred		0.058	T
GERP RS		-10
Varity_R		0.054
gMVP		0.093

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

Publications

LitVar

Other links and lift over

dbSNP: rs869801; hg19: chr10-129245684;