chr9-128225994-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.
| Apply | Criterion Code & Title / Strength | Rationale / Clinical Context | |
|---|---|---|---|
| PM2Absent/extremely low in population databases | 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. | ||
| BP4Computational evidence suggests no impact | 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.
RefSeq Transcripts
| Sel. | Gene / Transcript | Tags | HGVSc / HGVSp | Effect | Exon rank | Protein / UniProt |
|---|---|---|---|---|---|---|
DNM1 | MANE Select | c.1335+1605G>A | intron | Intron 10 of 21 | Prot: NP_004399.2 UniProt: | |
DNM1 | c.1335+1605G>A | intron | Intron 10 of 21 | Prot: NP_001361198.1 UniProt: | ||
DNM1 | c.1197-41G>A | intron | Intron 9 of 21 | Prot: NP_001275668.1 UniProt: |
Ensembl Transcripts
| Sel. | Gene / Transcript | Tags | HGVSc / HGVSp | Effect | Exon rank | Protein / UniProt |
|---|---|---|---|---|---|---|
DNM1 | TSL:1MANE Select | c.1335+1605G>A | intron | Intron 10 of 21 | Prot: ENSP00000362014.4 UniProt: | |
DNM1 | TSL:1 | c.1197-41G>A | intron | Intron 9 of 21 | Prot: ENSP00000420045.1 UniProt: | |
DNM1 | TSL:5 | c.1335+1605G>A | intron | Intron 10 of 21 | Prot: ENSP00000489096.1 UniProt: |
Frequencies
Allele frequencies (AF), counts (AC/AN), homozygotes and coverage
Common (AF > 0.05 / Hom > 5)
Rare (AF ≤ 0.0001 / Hom ≤ 1)
| Source / population | AF | AC | Hom | AN | Coverage |
|---|---|---|---|---|---|
Global population databases 3 sources | |||||
GnomAD3 genomes | Cov:31 | ||||
GnomAD4 exome | Cov:30 | ||||
GnomAD4 genome | Cov:31 | ||||
Showing 3 sources
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
| Algorithm | Calibrated pred. | Score | Prediction |
|---|---|---|---|
AlphaGenome AVI | Pathogenic | 25 | |
BayesDel_noAF | Benign | -0.82 | |
CADD | Benign | 14 | |
DANN | Benign | 0.70 | |
GPN-Star LLR | N/A | -5.3 | |
GPN-Star score | N/A | 5.3 | |
PhyloP100 | Benign | 0.44 |
Showing 7 of 7 scores
Splicing Scores
| Algorithm | Calibrated pred. | Score | Prediction |
|---|---|---|---|
Pangolin (max) | Pathogenic | 0.77 | |
Pangolin gain | Pathogenic | 0.77 | Position offset: 2 |
Showing 2 of 2 scores
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.
MaveDB functional evidence
No MaveDB functional evidence found for this variant.
Publications
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Other links and lift over
hg19: chr9-130988273;