dbSNP rs13285411: DNM1:c.1422+1482C>A (chr9-128235589-C-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004408.4(DNM1):c.1422+1482C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.164 in 152,098 control chromosomes in the GnomAD database, including 2,334 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.16 ( 2334 hom., cov: 32)

Consequence

DNM1
NM_004408.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.226

Publications

9 publications found

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 Gene-Disease associations (from GenCC):

genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
developmental and epileptic encephalopathy, 31A
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
developmental and epileptic encephalopathy, 31B
Inheritance: AR, AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
Lennox-Gastaut syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
undetermined early-onset epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

DNM1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.318 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DNM1	NM_004408.4 link	c.1422+1482C>A		intron_variant	Intron 11 of 21	ENST00000372923.8	NP_004399.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DNM1	ENST00000372923.8 link	c.1422+1482C>A		intron_variant	Intron 11 of 21	1	NM_004408.4	ENSP00000362014.4
DNM1	ENST00000634267.2 link	c.1422+1482C>A		intron_variant	Intron 11 of 21	5		ENSP00000489096.1

Frequencies

GnomAD3 genomes

AF:

0.164

AC:

24864

AN:

151980

Hom.:

2331

Cov.:

show subpopulations

Gnomad AFR

AF:

0.224

Gnomad AMI

AF:

0.118

Gnomad AMR

AF:

0.119

Gnomad ASJ

AF:

0.144

Gnomad EAS

AF:

0.331

Gnomad SAS

AF:

0.271

Gnomad FIN

AF:

0.132

Gnomad MID

AF:

0.165

Gnomad NFE

AF:

0.123

Gnomad OTH

AF:

0.161

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.164

AC:

24883

AN:

152098

Hom.:

2334

Cov.:

AF XY:

0.166

AC XY:

12337

AN XY:

74362

show subpopulations

African (AFR)

AF:

0.224

AC:

9264

AN:

41440

American (AMR)

AF:

0.119

AC:

1824

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

498

AN:

3468

East Asian (EAS)

AF:

0.331

AC:

1710

AN:

5170

South Asian (SAS)

AF:

0.270

AC:

1304

AN:

4826

European-Finnish (FIN)

AF:

0.132

AC:

1392

AN:

10582

Middle Eastern (MID)

AF:

0.160

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.123

AC:

8391

AN:

68000

Other (OTH)

AF:

0.163

AC:

345

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1034

2068

3102

4136

5170

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

284

568

852

1136

1420

<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:

0.136

Hom.:

2515

Bravo

AF:

0.161

Asia WGS

AF:

0.270

AC:

939

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

1.7

(source)

DANN

Benign

0.64

PhyloP100

-0.23

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over