chr19-10829116-T-C

Variant names:

Variant summary

Our verdict is Benign. Variant got -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 (★★).

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

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 [Likely_benign]. Clinvar id is 158523.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr19-10829116-T-C is described in Lovd as [Benign].

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	P50570-4Q8N1K8

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		P50570-4

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

GnomAD3 exomes

AF:

0.312

AC:

78204

AN:

250390

Hom.:

12924

AF XY:

0.313

AC XY:

42359

AN XY:

135494

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 SAS exome

AF:

0.313

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

Gnomad4 AFR exome

AF:

0.281

Gnomad4 AMR exome

AF:

0.255

Gnomad4 ASJ exome

AF:

0.313

Gnomad4 EAS exome

AF:

0.576

Gnomad4 SAS exome

AF:

0.309

Gnomad4 FIN exome

AF:

0.317

Gnomad4 NFE exome

AF:

0.300

Gnomad4 OTH exome

AF:

0.315

GnomAD4 genome

AF:

0.300

AC:

45696

AN:

152100

Hom.:

7084

Cov.:

AF XY:

0.305

AC XY:

22708

AN XY:

74356

show subpopulations

Gnomad4 AFR

AF:

0.280

Gnomad4 AMR

AF:

0.271

Gnomad4 ASJ

AF:

0.310

Gnomad4 EAS

AF:

0.578

Gnomad4 SAS

AF:

0.303

Gnomad4 FIN

AF:

0.342

Gnomad4 NFE

AF:

0.291

Gnomad4 OTH

AF:

0.297

Alfa

AF:

0.286

Hom.:

9848

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

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

Significance: Benign

Review Status: no assertion criteria provided

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). -

Aug 15, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 12, 2017

Athena Diagnostics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Clinical Genetics, Academic Medical Center

Significance: Benign

Review Status: no assertion criteria provided

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

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

DANN

Benign

0.45

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over