chr19-10718276-C-G
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4
The NM_001005361.3(DNM2):c.34C>G(p.Leu12Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control
Consequence
DNM2
NM_001005361.3 missense
NM_001005361.3 missense
Scores
3
8
8
Clinical Significance
Conservation
PhyloP100: 5.20
Publications
0 publications found
Genes affected
DNM2 (HGNC:2974): (dynamin 2) Dynamins represent one of the subfamilies of GTP-binding proteins. These proteins share considerable sequence similarity over the N-terminal portion of the molecule, which contains the GTPase domain. Dynamins are associated with microtubules. They have been implicated in cell processes such as endocytosis and cell motility, and in alterations of the membrane that accompany certain activities such as bone resorption by osteoclasts. Dynamins bind many proteins that bind actin and other cytoskeletal proteins. Dynamins can also self-assemble, a process that stimulates GTPase activity. Five alternatively spliced transcripts encoding different proteins have been described. Additional alternatively spliced transcripts may exist, but their full-length nature has not been determined. [provided by RefSeq, Jun 2010]
MIR638 (HGNC:32894): (microRNA 638) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]
Genome browser will be placed here
ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 1 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.34104925).
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1342892Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 662784
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1342892
Hom.:
Cov.:
31
AF XY:
AC XY:
0
AN XY:
662784
African (AFR)
AF:
AC:
0
AN:
27444
American (AMR)
AF:
AC:
0
AN:
29018
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
23430
East Asian (EAS)
AF:
AC:
0
AN:
29122
South Asian (SAS)
AF:
AC:
0
AN:
73942
European-Finnish (FIN)
AF:
AC:
0
AN:
47386
Middle Eastern (MID)
AF:
AC:
0
AN:
3928
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1053448
Other (OTH)
AF:
AC:
0
AN:
55174
GnomAD4 genome
GnomAD4 genome
Cov.:
33
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Uncertain:1
Sep 13, 2019
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The p.L12V variant (also known as c.34C>G), located in coding exon 1 of the DNM2 gene, results from a C to G substitution at nucleotide position 34. The leucine at codon 12 is replaced by valine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Benign
DEOGEN2
Uncertain
.;.;.;D;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Uncertain
D
MutationAssessor
Benign
N;N;N;N;N
PhyloP100
PrimateAI
Uncertain
T
PROVEAN
Benign
.;N;N;N;N
REVEL
Uncertain
Sift
Benign
.;T;T;T;T
Sift4G
Benign
T;T;T;T;T
Polyphen
1.0, 0.33
.;D;.;B;.
Vest4
MutPred
Gain of ubiquitination at K15 (P = 0.1047);Gain of ubiquitination at K15 (P = 0.1047);Gain of ubiquitination at K15 (P = 0.1047);Gain of ubiquitination at K15 (P = 0.1047);Gain of ubiquitination at K15 (P = 0.1047);
MVP
MPC
1.0
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
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.