Genetic Variant DTNA:c.-2+253_-2+256delGTGT (chr18-34710675-AGTGT-A) – 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+256delGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 147,868 control chromosomes in the GnomAD database, including 117 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.028 ( 117 hom., cov: 26)

Consequence

DTNA
NM_001386795.1 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.254

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-AGTGT-A is Benign according to our data. Variant chr18-34710675-AGTGT-A is described in ClinVar as Benign. ClinVar VariationId is 1273441.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 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+256delGTGT	intron	N/A	NP_001373724.1	A0A7P0TBH9
DTNA	NM_001386788.1		c.-2+253_-2+256delGTGT	intron	N/A	NP_001373717.1	Q9Y4J8-17
DTNA	NM_001198938.2		c.-2+31106_-2+31109delGTGT	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+231_-2+234delGTGT	intron	N/A	ENSP00000405819.2	Q9Y4J8-17
DTNA	ENST00000598334.5	TSL:1	c.-2+31084_-2+31087delGTGT	intron	N/A	ENSP00000470152.1	Q9Y4J8-15
DTNA	ENST00000399121.9	TSL:1	c.-2+31084_-2+31087delGTGT	intron	N/A	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes

AF:

0.0279

AC:

4125

AN:

147790

Hom.:

114

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0771

Gnomad AMI

AF:

0.0155

Gnomad AMR

AF:

0.00831

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.000791

Gnomad SAS

AF:

0.00346

Gnomad FIN

AF:

0.0116

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0104

Gnomad OTH

AF:

0.0184

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

GnomAD4 genome

AF:

0.0280

AC:

4144

AN:

147868

Hom.:

117

Cov.:

AF XY:

0.0278

AC XY:

2004

AN XY:

72072

show subpopulations

African (AFR)

AF:

0.0773

AC:

3144

AN:

40650

American (AMR)

AF:

0.00830

AC:

122

AN:

14700

Ashkenazi Jewish (ASJ)

AF:

0.000293

AC:

AN:

3412

East Asian (EAS)

AF:

0.000794

AC:

AN:

5040

South Asian (SAS)

AF:

0.00369

AC:

AN:

4606

European-Finnish (FIN)

AF:

0.0116

AC:

114

AN:

9792

Middle Eastern (MID)

AF:

0.00

AC:

AN:

288

European-Non Finnish (NFE)

AF:

0.0104

AC:

691

AN:

66446

Other (OTH)

AF:

0.0182

AC:

AN:

2032

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

199

399

598

798

997

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.00634

Hom.:

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

0.25

Mutation Taster

=100/0

polymorphism

(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

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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