19-10829116-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001005361.3(DNM2):c.2139T>C(p.Ala713Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.307 in 1,613,602 control chromosomes in the GnomAD database, including 78,330 homozygotes. 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. A713A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.30 ( 7084 hom., cov: 33)

Exomes 𝑓: 0.31 ( 71246 hom. )

Consequence

DNM2
NM_001005361.3 synonymous

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -4.76

Publications

32 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 links:

MIR6793 (HGNC:50251): (microRNA 6793) microRNAs (miRNAs) are short (20-24 nt) non-coding RNAs that are involved in post-transcriptional regulation of gene expression in multicellular organisms by affecting both the stability and translation of mRNAs. miRNAs are transcribed by RNA polymerase II as part of capped and polyadenylated primary transcripts (pri-miRNAs) that can be either protein-coding or non-coding. The primary transcript is cleaved by the Drosha ribonuclease III enzyme to produce an approximately 70-nt stem-loop precursor miRNA (pre-miRNA), which is further cleaved by the cytoplasmic Dicer ribonuclease to generate the mature miRNA and antisense miRNA star (miRNA*) products. The mature miRNA is incorporated into a RNA-induced silencing complex (RISC), which recognizes target mRNAs through imperfect base pairing with the miRNA and most commonly results in translational inhibition or destabilization of the target mRNA. The RefSeq represents the predicted microRNA stem-loop. [provided by RefSeq, Sep 2009]

MIR6793 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.91).

BP6

Variant 19-10829116-T-C is Benign according to our data. Variant chr19-10829116-T-C is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 158523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-4.76 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.561 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM2	NM_001005361.3 link	c.2139T>C	p.Ala713Ala	synonymous_variant	Exon 19 of 21	ENST00000389253.9	NP_001005361.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9 link	c.2139T>C	p.Ala713Ala	synonymous_variant	Exon 19 of 21	5	NM_001005361.3	ENSP00000373905.4

Frequencies

GnomAD3 genomes

AF:

0.300

AC:

45622

AN:

151982

Hom.:

7058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.279

Gnomad AMI

AF:

0.314

Gnomad AMR

AF:

0.271

Gnomad ASJ

AF:

0.310

Gnomad EAS

AF:

0.578

Gnomad SAS

AF:

0.303

Gnomad FIN

AF:

0.342

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.296

GnomAD2 exomes

AF:

0.312

AC:

78204

AN:

250390

AF XY:

0.313

show subpopulations

Gnomad AFR exome

AF:

0.281

Gnomad AMR exome

AF:

0.256

Gnomad ASJ exome

AF:

0.319

Gnomad EAS exome

AF:

0.564

Gnomad FIN exome

AF:

0.321

Gnomad NFE exome

AF:

0.291

Gnomad OTH exome

AF:

0.313

GnomAD4 exome

AF:

0.308

AC:

449698

AN:

1461502

Hom.:

71246

Cov.:

AF XY:

0.307

AC XY:

223397

AN XY:

727050

show subpopulations

African (AFR)

AF:

0.281

AC:

9419

AN:

33474

American (AMR)

AF:

0.255

AC:

11413

AN:

44672

Ashkenazi Jewish (ASJ)

AF:

0.313

AC:

8182

AN:

26134

East Asian (EAS)

AF:

0.576

AC:

22875

AN:

39682

South Asian (SAS)

AF:

0.309

AC:

26645

AN:

86238

European-Finnish (FIN)

AF:

0.317

AC:

16909

AN:

53272

Middle Eastern (MID)

AF:

0.337

AC:

1943

AN:

5768

European-Non Finnish (NFE)

AF:

0.300

AC:

333313

AN:

1111880

Other (OTH)

AF:

0.315

AC:

18999

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

22607

45214

67820

90427

113034

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11214

22428

33642

44856

56070

<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:

0.300

AC:

45696

AN:

152100

Hom.:

7084

Cov.:

AF XY:

0.305

AC XY:

22708

AN XY:

74356

show subpopulations

African (AFR)

AF:

0.280

AC:

11622

AN:

41502

American (AMR)

AF:

0.271

AC:

4150

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.310

AC:

1074

AN:

3468

East Asian (EAS)

AF:

0.578

AC:

2981

AN:

5158

South Asian (SAS)

AF:

0.303

AC:

1461

AN:

4822

European-Finnish (FIN)

AF:

0.342

AC:

3621

AN:

10582

Middle Eastern (MID)

AF:

0.360

AC:

105

AN:

292

European-Non Finnish (NFE)

AF:

0.291

AC:

19768

AN:

67964

Other (OTH)

AF:

0.297

AC:

628

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1636

3272

4907

6543

8179

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

470

940

1410

1880

2350

<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:

0.288

Hom.:

15448

Bravo

AF:

0.298

Asia WGS

AF:

0.419

AC:

1459

AN:

3478

EpiCase

AF:

0.303

EpiControl

AF:

0.296

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:6

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Nov 24, 2014

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Ala713Ala in exon 19 of DNM2: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 29.1% (2504/8600) of European American chromosomes from a broad population by the NHLBI Exome Sequen cing Project (http://evs.gs.washington.edu/EVS; dbSNP rs2229920). -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Jul 12, 2017

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Charcot-Marie-Tooth disease dominant intermediate B

Benign:2

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Autosomal dominant centronuclear myopathy

Benign:1

Jan 12, 2018

Illumina Laboratory Services, Illumina

Significance: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

-0.91

CADD

Benign

0.23

(source)

DANN

Benign

0.45

PhyloP100

-4.8

PromoterAI

-0.00020

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=96/4

polymorphism (auto)

(source)

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

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over