Variant rs2229917 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BA1

The NM_004408.4(DNM1):c.312G>A(p.Glu104=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.072 in 1,613,176 control chromosomes in the GnomAD database, including 5,489 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.11 ( 1342 hom., cov: 31)

Exomes 𝑓: 0.068 ( 4147 hom. )

Consequence

DNM1
NM_004408.4 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.62

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.2).

BP6

Variant 9-128218658-G-A is Benign according to our data. Variant chr9-128218658-G-A is described in ClinVar as [Benign]. Clinvar id is 380778.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=2.62 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.22 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DNM1	NM_004408.4 linkuse as main transcript	c.312G>A	p.Glu104=	synonymous_variant	3/22	ENST00000372923.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DNM1	ENST00000372923.8 linkuse as main transcript	c.312G>A	p.Glu104=	synonymous_variant	3/22	1	NM_004408.4	A1	Q05193-1

Frequencies

GnomAD3 genomes

AF:

0.109

AC:

16569

AN:

151940

Hom.:

1335

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.0559

Gnomad AMR

AF:

0.0745

Gnomad ASJ

AF:

0.117

Gnomad EAS

AF:

0.00309

Gnomad SAS

AF:

0.0702

Gnomad FIN

AF:

0.0394

Gnomad MID

AF:

0.146

Gnomad NFE

AF:

0.0693

Gnomad OTH

AF:

0.109

GnomAD3 exomes

AF:

0.0717

AC:

17944

AN:

250324

Hom.:

1001

AF XY:

0.0713

AC XY:

9652

AN XY:

135422

show subpopulations

Gnomad AFR exome

AF:

0.230

Gnomad AMR exome

AF:

0.0457

Gnomad ASJ exome

AF:

0.118

Gnomad EAS exome

AF:

0.00327

Gnomad SAS exome

AF:

0.0692

Gnomad FIN exome

AF:

0.0385

Gnomad NFE exome

AF:

0.0706

Gnomad OTH exome

AF:

0.0771

GnomAD4 exome

AF:

0.0681

AC:

99515

AN:

1461118

Hom.:

4147

Cov.:

AF XY:

0.0686

AC XY:

49865

AN XY:

726746

show subpopulations

Gnomad4 AFR exome

AF:

0.230

Gnomad4 AMR exome

AF:

0.0484

Gnomad4 ASJ exome

AF:

0.117

Gnomad4 EAS exome

AF:

0.00189

Gnomad4 SAS exome

AF:

0.0700

Gnomad4 FIN exome

AF:

0.0406

Gnomad4 NFE exome

AF:

0.0655

Gnomad4 OTH exome

AF:

0.0783

GnomAD4 genome

AF:

0.109

AC:

16605

AN:

152058

Hom.:

1342

Cov.:

AF XY:

0.105

AC XY:

7827

AN XY:

74326

show subpopulations

Gnomad4 AFR

AF:

0.224

Gnomad4 AMR

AF:

0.0743

Gnomad4 ASJ

AF:

0.117

Gnomad4 EAS

AF:

0.00309

Gnomad4 SAS

AF:

0.0701

Gnomad4 FIN

AF:

0.0394

Gnomad4 NFE

AF:

0.0693

Gnomad4 OTH

AF:

0.107

Alfa

AF:

0.0800

Hom.:

416

Bravo

AF:

0.115

Asia WGS

AF:

0.0600

AC:

209

AN:

3478

EpiCase

AF:

0.0768

EpiControl

AF:

0.0768

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 07, 2016

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Inborn genetic diseases

Benign:1

Benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Dec 31, 2015

This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Developmental and epileptic encephalopathy, 31

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.20

CADD

Benign

DANN

Benign

0.96

Splicing

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