Variant 18-34755951-A-G 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.-1-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,605,282 control chromosomes in the GnomAD database, including 5,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.077 ( 516 hom., cov: 33)

Exomes 𝑓: 0.075 ( 4517 hom. )

Consequence

DTNA
NM_001386795.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.369

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:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 1 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.86).

BP6

Variant 18-34755951-A-G is Benign according to our data. Variant chr18-34755951-A-G is described in ClinVar as [Benign]. Clinvar id is 192362.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0973 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.-1-25A>G		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.-1-25A>G		intron_variant		5	NM_001386795.1	ENSP00000405819	P3	Q9Y4J8-17
	ENST00000596954.1 linkuse as main transcript	n.314-316T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0767

AC:

11668

AN:

152162

Hom.:

514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0998

Gnomad AMI

AF:

0.145

Gnomad AMR

AF:

0.0436

Gnomad ASJ

AF:

0.0553

Gnomad EAS

AF:

0.000577

Gnomad SAS

AF:

0.0108

Gnomad FIN

AF:

0.0715

Gnomad MID

AF:

0.0253

Gnomad NFE

AF:

0.0822

Gnomad OTH

AF:

0.0616

GnomAD3 exomes

AF:

0.0603

AC:

14983

AN:

248488

Hom.:

610

AF XY:

0.0592

AC XY:

7949

AN XY:

134374

show subpopulations

Gnomad AFR exome

AF:

0.102

Gnomad AMR exome

AF:

0.0351

Gnomad ASJ exome

AF:

0.0474

Gnomad EAS exome

AF:

0.000602

Gnomad SAS exome

AF:

0.0123

Gnomad FIN exome

AF:

0.0771

Gnomad NFE exome

AF:

0.0828

Gnomad OTH exome

AF:

0.0594

GnomAD4 exome

AF:

0.0746

AC:

108375

AN:

1453002

Hom.:

4517

Cov.:

AF XY:

0.0726

AC XY:

52479

AN XY:

723238

show subpopulations

Gnomad4 AFR exome

AF:

0.104

Gnomad4 AMR exome

AF:

0.0361

Gnomad4 ASJ exome

AF:

0.0502

Gnomad4 EAS exome

AF:

0.000532

Gnomad4 SAS exome

AF:

0.0126

Gnomad4 FIN exome

AF:

0.0749

Gnomad4 NFE exome

AF:

0.0837

Gnomad4 OTH exome

AF:

0.0711

GnomAD4 genome

AF:

0.0767

AC:

11685

AN:

152280

Hom.:

516

Cov.:

AF XY:

0.0745

AC XY:

5546

AN XY:

74462

show subpopulations

Gnomad4 AFR

AF:

0.0998

Gnomad4 AMR

AF:

0.0436

Gnomad4 ASJ

AF:

0.0553

Gnomad4 EAS

AF:

0.000579

Gnomad4 SAS

AF:

0.0108

Gnomad4 FIN

AF:

0.0715

Gnomad4 NFE

AF:

0.0822

Gnomad4 OTH

AF:

0.0624

Alfa

AF:

0.0557

Hom.:

Bravo

AF:

0.0759

Asia WGS

AF:

0.0170

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:1

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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.86

CADD

Benign

0.20

DANN

Benign

0.29

La Branchor

0.35

BranchPoint Hunter

1.0

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