18-34710675-AGTGT-A

Position:

• chr18-34710675-AGTGT-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+253_-2+256del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 147,868 control chromosomes in the GnomAD database, including 117 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.028 (117 hom., cov: 26)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.254

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-AGTGT-A is Benign according to our data. Variant chr18-34710675-AGTGT-A is described in ClinVar as [Benign]. Clinvar id is 1273441.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.-2+253_-2+256del		intron_variant		ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.-2+253_-2+256del		intron_variant		5	NM_001386795.1	ENSP00000405819	P3

Frequencies

GnomAD3 genomes AF: 0.0279 AC: 4125 AN: 147790 Hom.: 114 Cov.: 26

Gnomad AFR AF: 0.0771

Gnomad AMI AF: 0.0155

Gnomad AMR AF: 0.00831

Gnomad ASJ AF: 0.000293

Gnomad EAS AF: 0.000791

Gnomad SAS AF: 0.00346

Gnomad FIN AF: 0.0116

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0104

Gnomad OTH AF: 0.0184

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

GnomAD4 genome AF: 0.0280 AC: 4144 AN: 147868 Hom.: 117 Cov.: 26 AF XY: 0.0278 AC XY: 2004 AN XY: 72072

Gnomad4 AFR AF: 0.0773

Gnomad4 AMR AF: 0.00830

Gnomad4 ASJ AF: 0.000293

Gnomad4 EAS AF: 0.000794

Gnomad4 SAS AF: 0.00369

Gnomad4 FIN AF: 0.0116

Gnomad4 NFE AF: 0.0104

Gnomad4 OTH AF: 0.0182

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 04, 2020

- -

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;