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GeneBe

2-224770222-T-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_014689.3(DOCK10):c.6433A>G(p.Met2145Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000699 in 1,431,398 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 7.0e-7 ( 0 hom. )

Consequence

DOCK10
NM_014689.3 missense

Scores

8
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
DOCK10NM_014689.3 linkuse as main transcriptc.6433A>G p.Met2145Val missense_variant 55/56 ENST00000258390.12

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
DOCK10ENST00000258390.12 linkuse as main transcriptc.6433A>G p.Met2145Val missense_variant 55/565 NM_014689.3 P3Q96BY6-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.99e-7
AC:
1
AN:
1431398
Hom.:
0
Cov.:
31
AF XY:
0.00000141
AC XY:
1
AN XY:
709316
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.11e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingAmbry GeneticsApr 07, 2022The c.6433A>G (p.M2145V) alteration is located in exon 55 (coding exon 55) of the DOCK10 gene. This alteration results from a A to G substitution at nucleotide position 6433, causing the methionine (M) at amino acid position 2145 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
0.45
BayesDel_addAF
Uncertain
0.075
D
BayesDel_noAF
Benign
-0.13
Cadd
Benign
23
Dann
Benign
0.97
Eigen
Benign
-0.11
Eigen_PC
Benign
0.090
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.97
D;D;D
M_CAP
Benign
0.018
T
MetaRNN
Uncertain
0.43
T;T;T
MetaSVM
Benign
-1.1
T
MutationTaster
Benign
1.0
D;D
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
-1.9
N;N;.
REVEL
Uncertain
0.29
Sift
Uncertain
0.0090
D;D;.
Sift4G
Benign
0.15
T;T;.
Polyphen
0.043
.;B;.
Vest4
0.78
MutPred
0.45
.;Loss of helix (P = 0.0626);.;
MVP
0.33
MPC
0.16
ClinPred
0.81
D
GERP RS
5.4
Varity_R
0.64
gMVP
0.54

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-225634939; API