chr18-34794183-A-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001386795.1(DTNA):c.295A>G(p.Thr99Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000335 in 1,613,886 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000036 ( 0 hom. )

Consequence

DTNA
NM_001386795.1 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: 9.29

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: Likely_benign. The variant received -4 ACMG points.

BS2

High AC in GnomAdExome4 at 53 AD gene.

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	HGVSp	Effect	Exon Rank	Protein	UniProt
DTNA	NM_001386795.1	MANE Select	c.295A>G	p.Thr99Ala	missense	Exon 4 of 23	NP_001373724.1	A0A7P0TBH9
DTNA	NM_001386788.1		c.295A>G	p.Thr99Ala	missense	Exon 4 of 23	NP_001373717.1	Q9Y4J8-17
DTNA	NM_001390.5		c.295A>G	p.Thr99Ala	missense	Exon 3 of 22	NP_001381.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DTNA	ENST00000444659.6	TSL:5 MANE Select	c.295A>G	p.Thr99Ala	missense	Exon 4 of 23	ENSP00000405819.2	Q9Y4J8-17
DTNA	ENST00000598334.5	TSL:1	c.295A>G	p.Thr99Ala	missense	Exon 5 of 20	ENSP00000470152.1	Q9Y4J8-15
DTNA	ENST00000399121.9	TSL:1	c.295A>G	p.Thr99Ala	missense	Exon 5 of 22	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes

AF:

0.00000658

AC:

AN:

152018

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000199

AC:

AN:

251342

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000440

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000363

AC:

AN:

1461868

Hom.:

Cov.:

AF XY:

0.0000358

AC XY:

AN XY:

727238

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33474

American (AMR)

AF:

0.00

AC:

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000116

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000414

AC:

AN:

1111998

Other (OTH)

AF:

0.0000994

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.00000658

AC:

AN:

152018

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74248

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

41388

American (AMR)

AF:

0.00

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.00

AC:

AN:

5178

South Asian (SAS)

AF:

0.00

AC:

AN:

4818

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000147

AC:

AN:

67986

Other (OTH)

AF:

0.00

AC:

AN:

2086

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000624

Hom.:

Bravo

AF:

0.00000756

ExAC

AF:

0.0000165

AC:

EpiCase

AF:

0.000109

EpiControl

AF:

0.00

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Left ventricular noncompaction 1 (1)

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.42

BayesDel_addAF

Uncertain

0.15

BayesDel_noAF

Uncertain

0.040

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.072

Eigen

Pathogenic

0.69

Eigen_PC

Pathogenic

0.71

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.052

MetaRNN

Uncertain

0.56

MetaSVM

Benign

-0.38

MutationAssessor

Uncertain

2.2

PhyloP100

9.3

PrimateAI

Uncertain

0.70

PROVEAN

Uncertain

-3.0

REVEL

Uncertain

0.44

Sift

Benign

0.17

Sift4G

Benign

0.19

Polyphen

1.0

Vest4

0.79

MutPred

0.26

Loss of loop (P = 0.1242)

MVP

0.70

MPC

0.96

ClinPred

0.92

GERP RS

5.4

Varity_R

0.41

gMVP

0.68

Mutation Taster

=42/58

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.020

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

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over