Genetic Variant NM_014689.3:c.6430G>A (chr2-224770225-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2BP4_StrongBP6_Moderate

The NM_014689.3(DOCK10):c.6430G>A(p.Val2144Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000208 in 1,439,966 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DOCK10
NM_014689.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.218

Publications

0 publications found

Variant links:

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]

DOCK10 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.02172178).

BP6

Variant 2-224770225-C-T is Benign according to our data. Variant chr2-224770225-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3504349.Status of the report is criteria_provided_single_submitter, 1 stars.

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DOCK10	NM_014689.3	MANE Select	c.6430G>A	p.Val2144Ile	missense	Exon 55 of 56	NP_055504.2	Q96BY6-1
DOCK10	NM_001363762.1		c.6469G>A	p.Val2157Ile	missense	Exon 55 of 56	NP_001350691.1	A0A2R8YD85
DOCK10	NM_001290263.2		c.6412G>A	p.Val2138Ile	missense	Exon 55 of 56	NP_001277192.1	Q96BY6-3

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DOCK10	ENST00000258390.12	TSL:5 MANE Select	c.6430G>A	p.Val2144Ile	missense	Exon 55 of 56	ENSP00000258390.7	Q96BY6-1
DOCK10	ENST00000409592.7	TSL:1	c.6412G>A	p.Val2138Ile	missense	Exon 55 of 56	ENSP00000386694.3	Q96BY6-3
DOCK10	ENST00000645028.1		c.6469G>A	p.Val2157Ile	missense	Exon 55 of 56	ENSP00000493664.1	A0A2R8YD85

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000208

AC:

AN:

1439966

Hom.:

Cov.:

AF XY:

0.00000280

AC XY:

AN XY:

714522

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32810

American (AMR)

AF:

0.00

AC:

AN:

41408

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24900

East Asian (EAS)

AF:

0.00

AC:

AN:

39260

South Asian (SAS)

AF:

0.0000122

AC:

AN:

81962

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52410

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5648

European-Non Finnish (NFE)

AF:

9.07e-7

AC:

AN:

1102002

Other (OTH)

AF:

0.0000168

AC:

AN:

59566

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.38

BayesDel_noAF

Benign

-0.78

CADD

Benign

0.79

(source)

DANN

Benign

0.31

DEOGEN2

Benign

0.016

Eigen

Benign

-1.7

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.070

LIST_S2

Benign

0.69

M_CAP

Benign

0.0081

MetaRNN

Benign

0.022

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-1.4

PhyloP100

0.22

PrimateAI

Benign

0.31

PROVEAN

Benign

0.52

REVEL

Benign

0.061

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0

Vest4

0.11

MutPred

0.44

Gain of helix (P = 0.1736)

MVP

0.14

MPC

0.13

ClinPred

0.028

GERP RS

-3.8

Varity_R

0.034

gMVP

0.041

Mutation Taster

=91/9

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over