chr2-224793441-A-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_014689.3(DOCK10):c.5171T>A(p.Ile1724Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,613,340 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00012 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000048 ( 0 hom. )
Consequence
DOCK10
NM_014689.3 missense
NM_014689.3 missense
Scores
8
5
4
Clinical Significance
Conservation
PhyloP100: 8.81
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 |
---|---|---|---|---|---|---|---|
DOCK10 | NM_014689.3 | c.5171T>A | p.Ile1724Asn | missense_variant | 46/56 | ENST00000258390.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK10 | ENST00000258390.12 | c.5171T>A | p.Ile1724Asn | missense_variant | 46/56 | 5 | NM_014689.3 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.000118 AC: 18AN: 152144Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.00000402 AC: 1AN: 248600Hom.: 0 AF XY: 0.00000741 AC XY: 1AN XY: 134864
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GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461196Hom.: 0 Cov.: 30 AF XY: 0.00000413 AC XY: 3AN XY: 726826
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GnomAD4 genome ? AF: 0.000118 AC: 18AN: 152144Hom.: 0 Cov.: 32 AF XY: 0.000148 AC XY: 11AN XY: 74330
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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 submitter | clinical testing | Ambry Genetics | Sep 26, 2023 | The c.5171T>A (p.I1724N) alteration is located in exon 46 (coding exon 46) of the DOCK10 gene. This alteration results from a T to A substitution at nucleotide position 5171, causing the isoleucine (I) at amino acid position 1724 to be replaced by an asparagine (N). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Pathogenic
D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D
MetaSVM
Benign
T
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
D;D;.
REVEL
Uncertain
Sift
Uncertain
D;D;.
Sift4G
Pathogenic
D;D;.
Polyphen
0.94
.;P;.
Vest4
MutPred
0.56
.;Gain of catalytic residue at I1724 (P = 0.017);.;
MVP
MPC
0.73
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at