Genetic Variant DTNA:c.-2+255_-2+256dupGT (chr18-34710675-A-AGT) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001386795.1(DTNA):c.-2+255_-2+256dupGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 147,878 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.030 ( 101 hom., cov: 26)

Consequence

DTNA
NM_001386795.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.161

Publications

0 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):

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
dilated cardiomyopathy
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

DTNA links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP6

Variant 18-34710675-A-AGT is Benign according to our data. Variant chr18-34710675-A-AGT is described in ClinVar as Benign. ClinVar VariationId is 1284129.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386795.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNA	NM_001386795.1	MANE Select	c.-2+255_-2+256dupGT	intron	N/A	NP_001373724.1	A0A7P0TBH9
DTNA	NM_001386788.1		c.-2+255_-2+256dupGT	intron	N/A	NP_001373717.1	Q9Y4J8-17
DTNA	NM_001198938.2		c.-2+31108_-2+31109dupGT	intron	N/A	NP_001185867.1	Q9Y4J8-15

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DTNA	ENST00000444659.6	TSL:5 MANE Select	c.-2+230_-2+231insGT	intron	N/A	ENSP00000405819.2	Q9Y4J8-17
DTNA	ENST00000598334.5	TSL:1	c.-2+31083_-2+31084insGT	intron	N/A	ENSP00000470152.1	Q9Y4J8-15
DTNA	ENST00000399121.9	TSL:1	c.-2+31083_-2+31084insGT	intron	N/A	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes

AF:

0.0298

AC:

4402

AN:

147794

Hom.:

101

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0578

Gnomad AMI

AF:

0.0200

Gnomad AMR

AF:

0.0136

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.0307

Gnomad SAS

AF:

0.0184

Gnomad FIN

AF:

0.0541

Gnomad MID

AF:

0.0194

Gnomad NFE

AF:

0.0143

Gnomad OTH

AF:

0.0239

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

GnomAD4 genome

AF:

0.0299

AC:

4418

AN:

147878

Hom.:

101

Cov.:

AF XY:

0.0310

AC XY:

2234

AN XY:

72084

show subpopulations

African (AFR)

AF:

0.0580

AC:

2358

AN:

40658

American (AMR)

AF:

0.0136

AC:

200

AN:

14702

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3412

East Asian (EAS)

AF:

0.0308

AC:

155

AN:

5038

South Asian (SAS)

AF:

0.0184

AC:

AN:

4612

European-Finnish (FIN)

AF:

0.0541

AC:

529

AN:

9770

Middle Eastern (MID)

AF:

0.0208

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0143

AC:

952

AN:

66464

Other (OTH)

AF:

0.0236

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

191

382

573

764

955

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<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:

0.0154

Hom.:

ClinVar

ClinVar submissions as Germline

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.16

Mutation Taster

=100/0

polymorphism

(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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over