2-224770272-T-G

Variant names:

• chr2-224770272-T-G
• NM_014689.3:c.6383A>C

Variant summary

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

The NM_014689.3(DOCK10):​c.6383A>C​(p.Glu2128Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. 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: DOCK10 NM_014689.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.48
• Publications: 0 publications found

Genes affected

DOCK10 (HGNC:23479): (dedicator of cytokinesis 10) This gene encodes a member of the dedicator of cytokinesis protein family. Members of this family are guanosine nucleotide exchange factors for Rho GTPases and defined by the presence of conserved DOCK-homology regions. The encoded protein belongs to the D (or Zizimin) subfamily of DOCK proteins, which also contain an N-terminal pleckstrin homology domain. Alternatively spliced transcript variants that encode different isoforms have been described. [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_014689.3. 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
	DOCK10	NM_014689.3	MANE Select	c.6383A>C	p.Glu2128Ala	missense	Exon 55 of 56	NP_055504.2	Q96BY6-1
	DOCK10	NM_001363762.1		c.6422A>C	p.Glu2141Ala	missense	Exon 55 of 56	NP_001350691.1	A0A2R8YD85
	DOCK10	NM_001290263.2		c.6365A>C	p.Glu2122Ala	missense	Exon 55 of 56	NP_001277192.1	Q96BY6-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DOCK10	ENST00000258390.12	TSL:5 MANE Select	c.6383A>C	p.Glu2128Ala	missense	Exon 55 of 56	ENSP00000258390.7	Q96BY6-1
	DOCK10	ENST00000409592.7	TSL:1	c.6365A>C	p.Glu2122Ala	missense	Exon 55 of 56	ENSP00000386694.3	Q96BY6-3
	DOCK10	ENST00000645028.1		c.6422A>C	p.Glu2141Ala	missense	Exon 55 of 56	ENSP00000493664.1	A0A2R8YD85

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

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	Benign	0.12
BayesDel_addAF	Benign	-0.056	T
BayesDel_noAF	Benign	-0.32
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.15	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.44
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Pathogenic	0.99	D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.46	T
MetaSVM	Benign	-0.90	T
MutationAssessor	Pathogenic	3.1	M
PhyloP100		3.5
PrimateAI	Uncertain	0.49	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.16
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0040	D
Polyphen		0.15	B
Vest4		0.39
MutPred		0.50		Loss of disorder (P = 0.0493)
MVP		0.47
MPC		0.40
ClinPred		0.99	D
GERP RS		5.4
Varity_R		0.78
gMVP		0.40
Mutation Taster		=75/25	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: chr2-225634989;