18-34710675-AGT-A

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001386795.1(DTNA):c.-2+255_-2+256del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.037 in 146,892 control chromosomes in the GnomAD database, including 272 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.037 (272 hom., cov: 26)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

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 -10 ACMG points.

• BP6: Variant 18-34710675-AGT-A is Benign according to our data. Variant chr18-34710675-AGT-A is described in ClinVar as [Benign]. Clinvar id is 1247380.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1	c.-2+255_-2+256del		intron_variant		ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.-2+255_-2+256del		intron_variant		5	NM_001386795.1	P3

Frequencies

GnomAD3 genomes AF: 0.0369 AC: 5415 AN: 146810 Hom.: 271 Cov.: 26

Gnomad AFR AF: 0.117

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0159

Gnomad ASJ AF: 0.0127

Gnomad EAS AF: 0.00199

Gnomad SAS AF: 0.00389

Gnomad FIN AF: 0.00371

Gnomad MID AF: 0.0130

Gnomad NFE AF: 0.00458

Gnomad OTH AF: 0.0239

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0370 AC: 5430 AN: 146892 Hom.: 272 Cov.: 26 AF XY: 0.0364 AC XY: 2606 AN XY: 71502

Gnomad4 AFR AF: 0.117

Gnomad4 AMR AF: 0.0159

Gnomad4 ASJ AF: 0.0127

Gnomad4 EAS AF: 0.00219

Gnomad4 SAS AF: 0.00391

Gnomad4 FIN AF: 0.00371

Gnomad4 NFE AF: 0.00459

Gnomad4 OTH AF: 0.0237

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs113472325; hg19: chr18-32290639;