18-34710675-AGTGTGTGTGTGT-AGTGTGTGTGT

Variant names:

• chr18-34710675-AGT-A
• rs113472325
• NM_001386795.1:c.-2+255_-2+256delGT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001386795.1(DTNA):​c.-2+255_-2+256delGT 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
• Publications: 0 publications found

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 Gene-Disease associations (from GenCC):

• left ventricular noncompaction 1

  Inheritance: AD Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• Meniere disease

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics
• congenital heart disease

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen
• dilated cardiomyopathy

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001386795.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	NM_001386795.1	MANE Select	c.-2+255_-2+256delGT		intron	N/A	NP_001373724.1	A0A7P0TBH9
	DTNA	NM_001386788.1		c.-2+255_-2+256delGT		intron	N/A	NP_001373717.1	Q9Y4J8-17
	DTNA	NM_001198938.2		c.-2+31108_-2+31109delGT		intron	N/A	NP_001185867.1	Q9Y4J8-15

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNA	ENST00000444659.6	TSL:5 MANE Select	c.-2+231_-2+232delGT		intron	N/A	ENSP00000405819.2	Q9Y4J8-17
	DTNA	ENST00000598334.5	TSL:1	c.-2+31084_-2+31085delGT		intron	N/A	ENSP00000470152.1	Q9Y4J8-15
	DTNA	ENST00000399121.9	TSL:1	c.-2+31084_-2+31085delGT		intron	N/A	ENSP00000382072.5	Q9Y4J8-14

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

African (AFR) AF: 0.117 AC: 4736 AN: 40598

American (AMR) AF: 0.0159 AC: 232 AN: 14558

Ashkenazi Jewish (ASJ) AF: 0.0127 AC: 43 AN: 3392

East Asian (EAS) AF: 0.00219 AC: 11 AN: 5016

South Asian (SAS) AF: 0.00391 AC: 18 AN: 4608

European-Finnish (FIN) AF: 0.00371 AC: 35 AN: 9426

Middle Eastern (MID) AF: 0.0140 AC: 4 AN: 286

European-Non Finnish (NFE) AF: 0.00459 AC: 303 AN: 66080

Other (OTH) AF: 0.0237 AC: 48 AN: 2026

Alfa AF: 0.000576 Hom.: 32

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.16
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs113472325; hg19: chr18-32290639; COSMIC: COSV52008169;