Genetic Variant DTNA:c.-2+253_-2+256dupGTGT (chr18-34710675-A-AGTGT) – 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+253_-2+256dupGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 147,864 control chromosomes in the GnomAD database, including 1,240 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.13 ( 1240 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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

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

BP6

Variant 18-34710675-A-AGTGT is Benign according to our data. Variant chr18-34710675-A-AGTGT is described in ClinVar as Benign. ClinVar VariationId is 1181084.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 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+253_-2+256dupGTGT	intron	N/A	NP_001373724.1	A0A7P0TBH9
DTNA	NM_001386788.1		c.-2+253_-2+256dupGTGT	intron	N/A	NP_001373717.1	Q9Y4J8-17
DTNA	NM_001198938.2		c.-2+31106_-2+31109dupGTGT	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+231insGTGT	intron	N/A	ENSP00000405819.2	Q9Y4J8-17
DTNA	ENST00000598334.5	TSL:1	c.-2+31083_-2+31084insGTGT	intron	N/A	ENSP00000470152.1	Q9Y4J8-15
DTNA	ENST00000399121.9	TSL:1	c.-2+31083_-2+31084insGTGT	intron	N/A	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes

AF:

0.127

AC:

18722

AN:

147780

Hom.:

1240

Cov.:

show subpopulations

Gnomad AFR

AF:

0.197

Gnomad AMI

AF:

0.0532

Gnomad AMR

AF:

0.0918

Gnomad ASJ

AF:

0.0750

Gnomad EAS

AF:

0.0348

Gnomad SAS

AF:

0.0988

Gnomad FIN

AF:

0.142

Gnomad MID

AF:

0.0935

Gnomad NFE

AF:

0.102

Gnomad OTH

AF:

0.117

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

GnomAD4 genome

AF:

0.127

AC:

18734

AN:

147864

Hom.:

1240

Cov.:

AF XY:

0.128

AC XY:

9187

AN XY:

72054

show subpopulations

African (AFR)

AF:

0.197

AC:

8008

AN:

40634

American (AMR)

AF:

0.0917

AC:

1348

AN:

14698

Ashkenazi Jewish (ASJ)

AF:

0.0750

AC:

256

AN:

3412

East Asian (EAS)

AF:

0.0347

AC:

175

AN:

5040

South Asian (SAS)

AF:

0.0981

AC:

452

AN:

4606

European-Finnish (FIN)

AF:

0.142

AC:

1391

AN:

9798

Middle Eastern (MID)

AF:

0.0972

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.102

AC:

6788

AN:

66454

Other (OTH)

AF:

0.118

AC:

240

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.498

Heterozygous variant carriers

764

1529

2293

3058

3822

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

210

420

630

840

1050

<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:

0.0479

Hom.:

Bravo

AF:

0.127

ClinVar

ClinVar submissions

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 (auto)

(source)

Splicing

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

Publications

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18-34710675-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGT

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