rs1617318

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001386795.1(DTNA):c.1743+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.324 in 1,594,552 control chromosomes in the GnomAD database, including 87,720 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.36 ( 10912 hom., cov: 32)

Exomes 𝑓: 0.32 ( 76808 hom. )

Consequence

DTNA
NM_001386795.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.923

Publications

11 publications found

Variant links:

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNA Gene-Disease associations (from GenCC):

dilated cardiomyopathy
Inheritance: AD Classification: LIMITED Submitted by: ClinGen
left ventricular noncompaction 1
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Meniere disease
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
congenital heart disease
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

DTNA links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 18-34864076-G-A is Benign according to our data. Variant chr18-34864076-G-A is described in ClinVar as Benign. ClinVar VariationId is 46416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.499 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNA	NM_001386795.1 link	c.1743+14G>A		intron_variant	Intron 17 of 22	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6 link	c.1743+14G>A		intron_variant	Intron 17 of 22	5	NM_001386795.1	ENSP00000405819.2		Q9Y4J8-17A0A7P0TBH9

Frequencies

GnomAD3 genomes

AF:

0.364

AC:

55261

AN:

151810

Hom.:

10869

Cov.:

show subpopulations

Gnomad AFR

AF:

0.504

Gnomad AMI

AF:

0.210

Gnomad AMR

AF:

0.263

Gnomad ASJ

AF:

0.316

Gnomad EAS

AF:

0.0486

Gnomad SAS

AF:

0.268

Gnomad FIN

AF:

0.364

Gnomad MID

AF:

0.339

Gnomad NFE

AF:

0.338

Gnomad OTH

AF:

0.346

GnomAD2 exomes

AF:

0.293

AC:

65653

AN:

224290

AF XY:

0.297

show subpopulations

Gnomad AFR exome

AF:

0.513

Gnomad AMR exome

AF:

0.167

Gnomad ASJ exome

AF:

0.322

Gnomad EAS exome

AF:

0.0480

Gnomad FIN exome

AF:

0.364

Gnomad NFE exome

AF:

0.334

Gnomad OTH exome

AF:

0.319

GnomAD4 exome

AF:

0.320

AC:

461132

AN:

1442624

Hom.:

76808

Cov.:

AF XY:

0.319

AC XY:

228387

AN XY:

716208

show subpopulations

African (AFR)

AF:

0.512

AC:

17005

AN:

33182

American (AMR)

AF:

0.179

AC:

7781

AN:

43472

Ashkenazi Jewish (ASJ)

AF:

0.317

AC:

8151

AN:

25720

East Asian (EAS)

AF:

0.0427

AC:

1680

AN:

39386

South Asian (SAS)

AF:

0.277

AC:

23267

AN:

83970

European-Finnish (FIN)

AF:

0.358

AC:

17739

AN:

49580

Middle Eastern (MID)

AF:

0.304

AC:

1746

AN:

5742

European-Non Finnish (NFE)

AF:

0.331

AC:

364613

AN:

1101914

Other (OTH)

AF:

0.321

AC:

19150

AN:

59658

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

16045

32091

48136

64182

80227

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11734

23468

35202

46936

58670

<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:

0.364

AC:

55358

AN:

151928

Hom.:

10912

Cov.:

AF XY:

0.361

AC XY:

26822

AN XY:

74260

show subpopulations

African (AFR)

AF:

0.505

AC:

20901

AN:

41380

American (AMR)

AF:

0.262

AC:

4010

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.316

AC:

1097

AN:

3468

East Asian (EAS)

AF:

0.0487

AC:

252

AN:

5178

South Asian (SAS)

AF:

0.268

AC:

1294

AN:

4822

European-Finnish (FIN)

AF:

0.364

AC:

3837

AN:

10542

Middle Eastern (MID)

AF:

0.333

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.338

AC:

22953

AN:

67946

Other (OTH)

AF:

0.344

AC:

725

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1693

3387

5080

6774

8467

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

524

1048

1572

2096

2620

<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:

0.339

Hom.:

25442

Bravo

AF:

0.361

Asia WGS

AF:

0.191

AC:

665

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 16, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jan 08, 2014

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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. -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Left ventricular noncompaction 1

Benign:1

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

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

-0.83

CADD

Benign

2.5

(source)

DANN

Benign

0.23

PhyloP100

0.92

Mutation Taster

=100/0

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