9-128225994-G-A
Variant names:
Variant summary
Our verdict is Likely benign. The variant received -2 classification points (ACMG Germline Pathogenicity v2019). PM2BP4_Strong
The NM_004408.4(DNM1):c.1335+1605G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant is absent from the gnomAD population database at sites with sufficient sequencing coverage. In-silico predictor (BayesDel (noAF)) classifies this variant as likely benign. Variant has been reported in ClinVar as Uncertain Significance (★★).
Frequency
Genomes: not found (cov: 31)
Consequence
DNM1
NM_004408.4 intron
NM_004408.4 intron
Scores
3
Clinical Significance
Conservation
PhyloP100: 0.443
Publications
0 publications found
Genes affected
DNM1 (HGNC:2972): (dynamin 1) This gene encodes a member of the dynamin subfamily of GTP-binding proteins. The encoded protein possesses unique mechanochemical properties used to tubulate and sever membranes, and is involved in clathrin-mediated endocytosis and other vesicular trafficking processes. Actin and other cytoskeletal proteins act as binding partners for the encoded protein, which can also self-assemble leading to stimulation of GTPase activity. More than sixty highly conserved copies of the 3' region of this gene are found elsewhere in the genome, particularly on chromosomes Y and 15. Alternatively spliced transcript variants encoding different isoforms have been described. [provided by RefSeq, Jul 2008]
DNM1 Gene-Disease associations (from GenCC):
- genetic developmental and epileptic encephalopathyInheritance: AR, AD Classification: DEFINITIVE, MODERATE Submitted by: ClinGen
- developmental and epileptic encephalopathy, 31AInheritance: AD Classification: STRONG, MODERATE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, PanelApp Australia
- developmental and epileptic encephalopathy, 31BInheritance: AR, AD Classification: STRONG, MODERATE Submitted by: PanelApp Australia, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
- Lennox-Gastaut syndromeInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
- undetermined early-onset epileptic encephalopathyInheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Genome browser will be placed here
new If you want to explore the variant's impact on the transcript NM_004408.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.
Classification according to ACMG Germline Pathogenicity v2019
Classification was made for transcript
Our verdict: Likely_benign. The variant received -2 points.
PM2
Absent from gnomAD (AD/XL gene) — PM2; Absent from gnomAD at well-covered site (MOI: AD+AR) (base 0.0001, raised to 0.00015 by highest known P/LP ClinVar AF 0.00015) — PM2 moderate.
BP4
Computational evidence supports benign — no pathogenic computational or splicing signal (BP4); No splicing predictor data available.; Germline computational verdict: benign (Strong).
Variant Effect in Transcripts
Automated classification analysis was done for transcript: NM_004408.4. You can select a different transcript below to see updated classification assignments.
Ensembl Transcripts
| Sel. | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DNM1 | TSL:1 MANE Select | c.1335+1605G>A | intron | N/A | ENSP00000362014.4 | Q05193-1 | |||
| DNM1 | TSL:1 | c.1197-41G>A | intron | N/A | ENSP00000420045.1 | Q05193-2 | |||
| DNM1 | TSL:5 | c.1335+1605G>A | intron | N/A | ENSP00000489096.1 | A0A0U1RQP1 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
31
GnomAD4 exome Cov.: 30
GnomAD4 exome
Cov.:
30
GnomAD4 genome
GnomAD4 genome
Cov.:
31
ClinVar
ClinVar submissions
View on ClinVar Significance:Uncertain significance
Revision:criteria provided, multiple submitters, no conflicts
Pathogenic
VUS
Benign
Condition
-
2
-
Developmental and epileptic encephalopathy, 31A (2)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
DANN
Benign
PhyloP100
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.
Publications
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Other links and lift over
hg19: chr9-130988273;