rs373161548

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2BP4_ModerateBP6_ModerateBP7

The NM_001005361.3(DNM2):c.2592C>A(p.Ala864Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000686 in 1,458,740 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 (★). Synonymous variant affecting the same amino acid position (i.e. A864A) has been classified as Likely benign.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

DNM2
NM_001005361.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.131

Publications

0 publications found

Variant links:

Genes affected

DNM2 (HGNC:2974): (dynamin 2) Dynamins represent one of the subfamilies of GTP-binding proteins. These proteins share considerable sequence similarity over the N-terminal portion of the molecule, which contains the GTPase domain. Dynamins are associated with microtubules. They have been implicated in cell processes such as endocytosis and cell motility, and in alterations of the membrane that accompany certain activities such as bone resorption by osteoclasts. Dynamins bind many proteins that bind actin and other cytoskeletal proteins. Dynamins can also self-assemble, a process that stimulates GTPase activity. Five alternatively spliced transcripts encoding different proteins have been described. Additional alternatively spliced transcripts may exist, but their full-length nature has not been determined. [provided by RefSeq, Jun 2010]

DNM2 Gene-Disease associations (from GenCC):

autosomal dominant centronuclear myopathy
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: ClinGen, Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)
Charcot-Marie-Tooth disease
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
Charcot-Marie-Tooth disease dominant intermediate B
Inheritance: AD Classification: STRONG, MODERATE, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
autosomal dominant Charcot-Marie-Tooth disease type 2M
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
fetal akinesia-cerebral and retinal hemorrhage syndrome
Inheritance: AR Classification: SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet
hereditary spastic paraplegia
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DNM2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 19-10831026-C-A is Benign according to our data. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr19-10831026-C-A is described in CliVar as Likely_benign. Clinvar id is 1517010.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-0.131 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM2	NM_001005361.3 link	c.2592C>A	p.Ala864Ala	synonymous_variant	Exon 21 of 21	ENST00000389253.9	NP_001005361.1	P50570-4Q8N1K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9 link	c.2592C>A	p.Ala864Ala	synonymous_variant	Exon 21 of 21	5	NM_001005361.3	ENSP00000373905.4		P50570-4

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000417

AC:

AN:

239984

AF XY:

0.00

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:

0.00000936

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1458740

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725422

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44498

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25988

East Asian (EAS)

AF:

0.00

AC:

AN:

39602

South Asian (SAS)

AF:

0.00

AC:

AN:

85492

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53118

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5760

European-Non Finnish (NFE)

AF:

9.00e-7

AC:

AN:

1110688

Other (OTH)

AF:

0.00

AC:

AN:

60198

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

Cov.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Charcot-Marie-Tooth disease dominant intermediate B

Benign:1

Jul 26, 2022

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.29

CADD

Benign

(source)

DANN

Benign

0.89

PhyloP100

-0.13

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over