Variant 18-34864076-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -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

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 46416.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34864076-G-A is described in Lovd as [Benign].

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/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1 linkuse as main transcript	c.1743+14G>A		intron_variant		ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6 linkuse as main transcript	c.1743+14G>A		intron_variant		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

GnomAD3 exomes

AF:

0.293

AC:

65653

AN:

224290

Hom.:

10734

AF XY:

0.297

AC XY:

35874

AN XY:

120812

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 SAS exome

AF:

0.275

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

Gnomad4 AFR exome

AF:

0.512

Gnomad4 AMR exome

AF:

0.179

Gnomad4 ASJ exome

AF:

0.317

Gnomad4 EAS exome

AF:

0.0427

Gnomad4 SAS exome

AF:

0.277

Gnomad4 FIN exome

AF:

0.358

Gnomad4 NFE exome

AF:

0.331

Gnomad4 OTH exome

AF:

0.321

GnomAD4 genome

AF:

0.364

AC:

55358

AN:

151928

Hom.:

10912

Cov.:

AF XY:

0.361

AC XY:

26822

AN XY:

74260

show subpopulations

Gnomad4 AFR

AF:

0.505

Gnomad4 AMR

AF:

0.262

Gnomad4 ASJ

AF:

0.316

Gnomad4 EAS

AF:

0.0487

Gnomad4 SAS

AF:

0.268

Gnomad4 FIN

AF:

0.364

Gnomad4 NFE

AF:

0.338

Gnomad4 OTH

AF:

0.344

Alfa

AF:

0.337

Hom.:

11440

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

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 08, 2014	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Sep 16, 2011	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Left ventricular noncompaction 1

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

2.5

DANN

Benign

0.23

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over