18-34710675-AGTGTGTGTGTGT-AGTGTGT

Variant names:

• chr18-34710675-AGTGTGT-A
• rs113472325
• NM_001386795.1:c.-2+251_-2+256delGTGTGT

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001386795.1(DTNA):​c.-2+251_-2+256delGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00208 in 147,938 control chromosomes in the GnomAD database, including 2 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0021 (2 hom., cov: 26)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.42
• 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: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAd4 at 308 AD gene.

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+251_-2+256delGTGTGT		intron	N/A	NP_001373724.1	A0A7P0TBH9
	DTNA	NM_001386788.1		c.-2+251_-2+256delGTGTGT		intron	N/A	NP_001373717.1	Q9Y4J8-17
	DTNA	NM_001198938.2		c.-2+31104_-2+31109delGTGTGT		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+236delGTGTGT		intron	N/A	ENSP00000405819.2	Q9Y4J8-17
	DTNA	ENST00000598334.5	TSL:1	c.-2+31084_-2+31089delGTGTGT		intron	N/A	ENSP00000470152.1	Q9Y4J8-15
	DTNA	ENST00000399121.9	TSL:1	c.-2+31084_-2+31089delGTGTGT		intron	N/A	ENSP00000382072.5	Q9Y4J8-14

Frequencies

GnomAD3 genomes AF: 0.00207 AC: 306 AN: 147854 Hom.: 2 Cov.: 26

Gnomad AFR AF: 0.00720

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000681

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00323

Gnomad NFE AF: 0.0000301

Gnomad OTH AF: 0.000497

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

GnomAD4 genome AF: 0.00208 AC: 308 AN: 147938 Hom.: 2 Cov.: 26 AF XY: 0.00216 AC XY: 156 AN XY: 72108

African (AFR) AF: 0.00723 AC: 294 AN: 40672

American (AMR) AF: 0.000680 AC: 10 AN: 14702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3412

East Asian (EAS) AF: 0.00 AC: 0 AN: 5040

South Asian (SAS) AF: 0.00 AC: 0 AN: 4612

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9800

Middle Eastern (MID) AF: 0.00347 AC: 1 AN: 288

European-Non Finnish (NFE) AF: 0.0000301 AC: 2 AN: 66476

Other (OTH) AF: 0.000492 AC: 1 AN: 2034

Alfa AF: 0.00 Hom.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.4
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs113472325; hg19: chr18-32290639;