dbSNP rs2229917: DNM1:p.Glu104Glu (chr9-128218658-G-A) – ACMG Classification: Benign (-19 pts)

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004408.4(DNM1):c.312G>A(p.Glu104Glu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 1,613,176 control chromosomes in the GnomAD database, including 5,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1342 hom., cov: 31)

Exomes 𝑓: 0.068 ( 4147 hom. )

Consequence

DNM1
NM_004408.4 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 2.62

Publications

9 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: AR, AD Classification: DEFINITIVE, MODERATE 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: G2P, Ambry Genetics, 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

DNM1 links:

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.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.2).

BP6

Variant 9-128218658-G-A is Benign according to our data. Variant chr9-128218658-G-A is described in ClinVar as Benign. ClinVar VariationId is 380778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004408.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNM1	NM_004408.4	MANE Select	c.312G>A	p.Glu104Glu	synonymous	Exon 3 of 22	NP_004399.2	Q05193-1
DNM1	NM_001374269.1		c.312G>A	p.Glu104Glu	synonymous	Exon 3 of 22	NP_001361198.1	A0A994J7J4
DNM1	NM_001288739.2		c.312G>A	p.Glu104Glu	synonymous	Exon 3 of 22	NP_001275668.1	Q05193-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DNM1	ENST00000372923.8	TSL:1 MANE Select	c.312G>A	p.Glu104Glu	synonymous	Exon 3 of 22	ENSP00000362014.4	Q05193-1
DNM1	ENST00000486160.3	TSL:1	c.312G>A	p.Glu104Glu	synonymous	Exon 3 of 22	ENSP00000420045.1	Q05193-2
DNM1	ENST00000634267.2	TSL:5	c.312G>A	p.Glu104Glu	synonymous	Exon 3 of 22	ENSP00000489096.1	A0A0U1RQP1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16569

AN:

151940

Hom.:

1335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0745

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0702

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0693

Gnomad OTH

AF:

0.109

GnomAD2 exomes

AF:

0.0717

AC:

17944

AN:

250324

AF XY:

0.0713

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.0457

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.00327

Gnomad FIN exome

AF:

0.0385

Gnomad NFE exome

AF:

0.0706

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0681

AC:

99515

AN:

1461118

Hom.:

4147

Cov.:

AF XY:

0.0686

AC XY:

49865

AN XY:

726746

show subpopulations

African (AFR)

AF:

0.230

AC:

7707

AN:

33458

American (AMR)

AF:

0.0484

AC:

2160

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

3050

AN:

26122

East Asian (EAS)

AF:

0.00189

AC:

AN:

39690

South Asian (SAS)

AF:

0.0700

AC:

6034

AN:

86198

European-Finnish (FIN)

AF:

0.0406

AC:

2162

AN:

53304

Middle Eastern (MID)

AF:

0.135

AC:

778

AN:

5766

European-Non Finnish (NFE)

AF:

0.0655

AC:

72825

AN:

1111544

Other (OTH)

AF:

0.0783

AC:

4724

AN:

60364

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

5529

11058

16586

22115

27644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2734

5468

8202

10936

13670

<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:

0.109

AC:

16605

AN:

152058

Hom.:

1342

Cov.:

AF XY:

0.105

AC XY:

7827

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.224

AC:

9257

AN:

41398

American (AMR)

AF:

0.0743

AC:

1137

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.117

AC:

407

AN:

3468

East Asian (EAS)

AF:

0.00309

AC:

AN:

5172

South Asian (SAS)

AF:

0.0701

AC:

338

AN:

4824

European-Finnish (FIN)

AF:

0.0394

AC:

418

AN:

10602

Middle Eastern (MID)

AF:

0.143

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0693

AC:

4712

AN:

67978

Other (OTH)

AF:

0.107

AC:

227

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

737

1475

2212

2950

3687

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

174

348

522

696

870

<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:

0.0808

Hom.:

536

Bravo

AF:

0.115

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.0768

EpiControl

AF:

0.0768

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (2)

Developmental and epileptic encephalopathy, 31A (1)

Inborn genetic diseases (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

(source)

DANN

Benign

0.96

PhyloP100

2.6

Mutation Taster

=94/6

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over