rs769121301

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_004408.4(DNM1):​c.1893+9C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000201 in 1,595,990 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000019 ( 0 hom. )

Consequence

DNM1
NM_004408.4 intron

Scores

2

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.373

Publications

0 publications found
Variant links:
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 encephalopathy
    Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 31A
    Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
  • developmental and epileptic encephalopathy, 31B
    Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
  • Lennox-Gastaut syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • undetermined early-onset epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.8).
BP6
Variant 9-128247495-C-A is Benign according to our data. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-128247495-C-A is described in CliVar as Likely_benign. Clinvar id is 508423.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DNM1NM_004408.4 linkc.1893+9C>A intron_variant Intron 17 of 21 ENST00000372923.8 NP_004399.2 Q05193-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DNM1ENST00000372923.8 linkc.1893+9C>A intron_variant Intron 17 of 21 1 NM_004408.4 ENSP00000362014.4 Q05193-1
DNM1ENST00000634267.2 linkc.1893+9C>A intron_variant Intron 17 of 21 5 ENSP00000489096.1 A0A0U1RQP1

Frequencies

GnomAD3 genomes
AF:
0.0000263
AC:
4
AN:
152144
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000441
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.0000206
AC:
5
AN:
242754
AF XY:
0.0000228
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000456
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000194
AC:
28
AN:
1443846
Hom.:
0
Cov.:
28
AF XY:
0.0000209
AC XY:
15
AN XY:
716580
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
33186
American (AMR)
AF:
0.00
AC:
0
AN:
43948
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
25930
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39272
South Asian (SAS)
AF:
0.00
AC:
0
AN:
85304
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53098
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5720
European-Non Finnish (NFE)
AF:
0.0000219
AC:
24
AN:
1097790
Other (OTH)
AF:
0.0000671
AC:
4
AN:
59598
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.502
Heterozygous variant carriers
0
2
3
5
6
8
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152144
Hom.:
0
Cov.:
32
AF XY:
0.0000135
AC XY:
1
AN XY:
74332
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
41428
American (AMR)
AF:
0.0000654
AC:
1
AN:
15282
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3468
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5198
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4828
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10608
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.0000441
AC:
3
AN:
68020
Other (OTH)
AF:
0.00
AC:
0
AN:
2090
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.475
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
Alfa
AF:
0.0000658
Hom.:
0
Bravo
AF:
0.0000264

ClinVar

Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 31A Benign:1
Dec 24, 2024
Labcorp Genetics (formerly Invitae), Labcorp
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

not specified Benign:1
Mar 29, 2017
GeneDx
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not provided Benign:1
Aug 14, 2018
Athena Diagnostics
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.80
CADD
Benign
10
DANN
Benign
0.62
PhyloP100
-0.37
Mutation Taster
=100/0
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs769121301; hg19: chr9-131009774; API