Variant 19-10806008-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001005361.3(DNM2):c.1545+41C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.168 in 1,613,244 control chromosomes in the GnomAD database, including 24,287 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.13 ( 1613 hom., cov: 32)

Exomes 𝑓: 0.17 ( 22674 hom. )

Consequence

DNM2
NM_001005361.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.79

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 19-10806008-C-T is Benign according to our data. Variant chr19-10806008-C-T is described in ClinVar as [Benign]. Clinvar id is 256865.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.174 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DNM2	NM_001005361.3 link	c.1545+41C>T		intron_variant		ENST00000389253.9	NP_001005361.1	P50570-4Q8N1K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DNM2	ENST00000389253.9 link	c.1545+41C>T		intron_variant		5	NM_001005361.3	ENSP00000373905.4		P50570-4

Frequencies

GnomAD3 genomes

AF:

0.130

AC:

19810

AN:

152070

Hom.:

1613

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0367

Gnomad AMI

AF:

0.261

Gnomad AMR

AF:

0.123

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.168

Gnomad SAS

AF:

0.127

Gnomad FIN

AF:

0.155

Gnomad MID

AF:

0.225

Gnomad NFE

AF:

0.177

Gnomad OTH

AF:

0.132

GnomAD3 exomes

AF:

0.147

AC:

36851

AN:

250128

Hom.:

2972

AF XY:

0.151

AC XY:

20475

AN XY:

135320

show subpopulations

Gnomad AFR exome

AF:

0.0353

Gnomad AMR exome

AF:

0.0900

Gnomad ASJ exome

AF:

0.204

Gnomad EAS exome

AF:

0.154

Gnomad SAS exome

AF:

0.143

Gnomad FIN exome

AF:

0.141

Gnomad NFE exome

AF:

0.176

Gnomad OTH exome

AF:

0.165

GnomAD4 exome

AF:

0.172

AC:

251988

AN:

1461056

Hom.:

22674

Cov.:

AF XY:

0.172

AC XY:

125123

AN XY:

726856

show subpopulations

Gnomad4 AFR exome

AF:

0.0320

Gnomad4 AMR exome

AF:

0.0908

Gnomad4 ASJ exome

AF:

0.202

Gnomad4 EAS exome

AF:

0.164

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.138

Gnomad4 NFE exome

AF:

0.184

Gnomad4 OTH exome

AF:

0.161

GnomAD4 genome

AF:

0.130

AC:

19807

AN:

152188

Hom.:

1613

Cov.:

AF XY:

0.132

AC XY:

9807

AN XY:

74392

show subpopulations

Gnomad4 AFR

AF:

0.0366

Gnomad4 AMR

AF:

0.123

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.169

Gnomad4 SAS

AF:

0.127

Gnomad4 FIN

AF:

0.155

Gnomad4 NFE

AF:

0.177

Gnomad4 OTH

AF:

0.134

Alfa

AF:

0.172

Hom.:

4068

Bravo

AF:

0.125

Asia WGS

AF:

0.123

AC:

431

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 26, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.050

DANN

Benign

0.71

RBP_binding_hub_radar

0.67

RBP_regulation_power_radar

3.2

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