chr2-224774964-A-C

Variant summary

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

The NM_014689.3(DOCK10):​c.5954T>G​(p.Leu1985Arg) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,504 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DOCK10
NM_014689.3 missense

Scores

1
6
12

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.29
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]

Genome browser will be placed here

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 rank MANE Protein UniProt
DOCK10NM_014689.3 linkc.5954T>G p.Leu1985Arg missense_variant Exon 52 of 56 ENST00000258390.12 NP_055504.2 Q96BY6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DOCK10ENST00000258390.12 linkc.5954T>G p.Leu1985Arg missense_variant Exon 52 of 56 5 NM_014689.3 ENSP00000258390.7 Q96BY6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.85e-7
AC:
1
AN:
1459504
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
725798
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.0000225
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:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Jan 31, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.5954T>G (p.L1985R) alteration is located in exon 52 (coding exon 52) of the DOCK10 gene. This alteration results from a T to G substitution at nucleotide position 5954, causing the leucine (L) at amino acid position 1985 to be replaced by an arginine (R). 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
Benign
0.21
BayesDel_addAF
Uncertain
0.12
D
BayesDel_noAF
Uncertain
-0.060
CADD
Benign
23
DANN
Benign
0.94
DEOGEN2
Benign
0.020
.;T;.
Eigen
Benign
0.010
Eigen_PC
Benign
0.076
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Uncertain
0.89
D;D;D
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.49
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Uncertain
2.2
.;M;.
PrimateAI
Pathogenic
0.81
D
PROVEAN
Benign
-1.9
N;N;.
REVEL
Benign
0.22
Sift
Benign
0.42
T;T;.
Sift4G
Benign
0.35
T;T;.
Polyphen
0.44
.;B;.
Vest4
0.65
MutPred
0.52
.;Gain of disorder (P = 0.017);.;
MVP
0.38
MPC
0.70
ClinPred
0.89
D
GERP RS
4.3
Varity_R
0.53
gMVP
0.57

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: chr2-225639681; API