rs1617318

chr18-34864076-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

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
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.923

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 -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	UniProt
DTNA	NM_001386795.1	c.1743+14G>A		intron_variant		ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.1743+14G>A		intron_variant		5	NM_001386795.1	P3

Frequencies

GnomAD3 genomes AF: 0.364 AC: 55261 AN: 151810 Hom.: 10869 Cov.: 32

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

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.: 32 AF XY: 0.319 AC XY: 228387 AN XY: 716208

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.: 32 AF XY: 0.361 AC XY: 26822 AN XY: 74260

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:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
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	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. -

Left ventricular noncompaction 1 Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

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

Other links and lift over

dbSNP: rs1617318; hg19: chr18-32444040; COSMIC: COSV51995587;