rs1363606775

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_ModerateBP6_Moderate

The NM_004408.4(DNM1):c.2360C>T(p.Ala787Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000635 in 1,417,620 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 Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A787T) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000055 ( 0 hom. )

Consequence

DNM1
NM_004408.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.43

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

DNM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.2632565).

BP6

Variant 9-128250766-C-T is Benign according to our data. Variant chr9-128250766-C-T is described in ClinVar as Benign. ClinVar VariationId is 476063.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1	NM_004408.4 link	c.2360C>T	p.Ala787Val	missense_variant	Exon 21 of 22	ENST00000372923.8	NP_004399.2	Q05193-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8 link	c.2360C>T	p.Ala787Val	missense_variant	Exon 21 of 22	1	NM_004408.4	ENSP00000362014.4		Q05193-1
DNM1	ENST00000634267.2 link	c.2360C>T	p.Ala787Val	missense_variant	Exon 21 of 22	5		ENSP00000489096.1		A0A0U1RQP1

Frequencies

GnomAD3 genomes

AF:

0.0000132

AC:

AN:

151772

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000295

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00

AC:

AN:

46086

AF XY:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000553

AC:

AN:

1265848

Hom.:

Cov.:

AF XY:

0.00000321

AC XY:

AN XY:

622308

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

25332

American (AMR)

AF:

0.00

AC:

AN:

19104

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

20280

East Asian (EAS)

AF:

0.00

AC:

AN:

27502

South Asian (SAS)

AF:

0.00

AC:

AN:

63214

European-Finnish (FIN)

AF:

0.00

AC:

AN:

31362

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3732

European-Non Finnish (NFE)

AF:

0.00000684

AC:

AN:

1023212

Other (OTH)

AF:

0.00

AC:

AN:

52110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.0000132

AC:

AN:

151772

Hom.:

Cov.:

AF XY:

0.0000270

AC XY:

AN XY:

74130

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41346

American (AMR)

AF:

0.00

AC:

AN:

15250

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5144

South Asian (SAS)

AF:

0.00

AC:

AN:

4830

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10558

Middle Eastern (MID)

AF:

0.00

AC:

AN:

310

European-Non Finnish (NFE)

AF:

0.0000295

AC:

AN:

67870

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Developmental and epileptic encephalopathy, 31A

Benign:1

Apr 25, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Uncertain

0.10

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.27

T;.;.;.;.;.;T;.;.

Eigen

Benign

-0.089

Eigen_PC

Benign

0.089

FATHMM_MKL

Uncertain

0.92

LIST_S2

Uncertain

0.86

D;.;.;T;D;D;D;T;T

M_CAP

Pathogenic

0.88

MetaRNN

Benign

0.26

T;T;T;T;T;T;T;T;T

MetaSVM

Uncertain

-0.058

MutationAssessor

Benign

0.71

N;N;N;N;.;N;.;N;.

PhyloP100

4.4

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

-0.70

N;N;N;N;.;N;.;.;.

REVEL

Uncertain

0.33

Sift

Benign

0.44

T;T;T;T;.;T;.;.;.

Sift4G

Benign

0.28

T;T;T;T;T;T;T;T;T

Polyphen

0.18

B;.;B;.;.;.;.;B;.

Vest4

0.20

MutPred

0.24

Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);.;Gain of relative solvent accessibility (P = 0.0082);.;Gain of relative solvent accessibility (P = 0.0082);Gain of relative solvent accessibility (P = 0.0082);

MVP

0.72

MPC

1.3

ClinPred

0.47

GERP RS

4.4

PromoterAI

-0.085

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.18

gMVP

0.17

Mutation Taster

=91/9

polymorphism

(source)

Splicing

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over