rs76713874

chr18-34879733-G-Achr18-34879733-G-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001386795.1(DTNA):c.2162+14G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0092 in 1,613,800 control chromosomes in the GnomAD database, including 84 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0079 (12 hom., cov: 32)
  • Exomes 𝑓: 0.0093 (72 hom.)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:7
• Conservation: PhyloP100: -1.32

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]

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 18-34879733-G-A is Benign according to our data. Variant chr18-34879733-G-A is described in ClinVar as [Benign]. Clinvar id is 36028.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34879733-G-A is described in Lovd as [Likely_benign]. Variant chr18-34879733-G-A is described in Lovd as [Benign].
• BS2: High AC in GnomAd at 1202 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1	c.2162+14G>A		intron_variant		ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.2162+14G>A		intron_variant		5	NM_001386795.1	P3

Frequencies

GnomAD3 genomes AF: 0.00790 AC: 1202 AN: 152136 Hom.: 12 Cov.: 32

Gnomad AFR AF: 0.00135

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00445

Gnomad ASJ AF: 0.0132

Gnomad EAS AF: 0.000193

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.0177

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0122

Gnomad OTH AF: 0.00335

GnomAD3 exomes AF: 0.00727 AC: 1824 AN: 251018 Hom.: 13 AF XY: 0.00740 AC XY: 1004 AN XY: 135662

Gnomad AFR exome AF: 0.00136

Gnomad AMR exome AF: 0.00188

Gnomad ASJ exome AF: 0.0109

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00164

Gnomad FIN exome AF: 0.0187

Gnomad NFE exome AF: 0.00987

Gnomad OTH exome AF: 0.00832

GnomAD4 exome AF: 0.00934 AC: 13652 AN: 1461546 Hom.: 72 Cov.: 30 AF XY: 0.00931 AC XY: 6766 AN XY: 727052

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.00235

Gnomad4 ASJ exome AF: 0.0129

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.00178

Gnomad4 FIN exome AF: 0.0184

Gnomad4 NFE exome AF: 0.0103

Gnomad4 OTH exome AF: 0.00851

GnomAD4 genome AF: 0.00789 AC: 1202 AN: 152254 Hom.: 12 Cov.: 32 AF XY: 0.00783 AC XY: 583 AN XY: 74430

Gnomad4 AFR AF: 0.00135

Gnomad4 AMR AF: 0.00445

Gnomad4 ASJ AF: 0.0132

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00104

Gnomad4 FIN AF: 0.0177

Gnomad4 NFE AF: 0.0122

Gnomad4 OTH AF: 0.00331

Alfa AF: 0.0100 Hom.: 7

Bravo AF: 0.00629

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:7

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Left ventricular noncompaction 1 Benign:4

Likely benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	Aug 22, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Invitae	Jan 29, 2024	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 12, 2022	- -

not specified Benign:2

Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Jul 02, 2012	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 12, 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. -

Cardiomyopathy Benign:1

Benign, no assertion criteria provided

clinical testing

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Jun 04, 2015

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
Cadd	Benign	0.67
Dann	Benign	0.63

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs76713874; hg19: chr18-32459697;