rs8092794

Variant names:

• chr18-34496273-G-A
• rs8092794
• ENST00000598774.6:c.-127+2759G>A

Your query was ambiguous. Multiple possible variants found:

• chr18-34496273-G-A
• chr18-34496273-G-C
• chr18-34496273-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000598774.6(DTNA):​c.-127+2759G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.654 in 150,930 control chromosomes in the GnomAD database, including 32,519 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.65 (32519 hom., cov: 28)
• Consequence: DTNA ENST00000598774.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420
• Publications: 5 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):

• dilated cardiomyopathy

  Inheritance: AD Classification: LIMITED Submitted by: ClinGen
• left ventricular noncompaction 1

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

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

  Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.751 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNA	NM_001386754.1	c.-127+2759G>A		intron_variant	Intron 1 of 21		NP_001373683.1
DTNA	NM_001386755.1	c.-127+2759G>A		intron_variant	Intron 1 of 21		NP_001373684.1
DTNA	NM_001386760.1	c.-127+2759G>A		intron_variant	Intron 1 of 21		NP_001373689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000598774.6	c.-127+2759G>A		intron_variant	Intron 1 of 16	1		ENSP00000472031.1
DTNA	ENST00000315456.10	c.-127+2759G>A		intron_variant	Intron 1 of 12	1		ENSP00000322519.5
DTNA	ENST00000684266.1	c.-127+2759G>A		intron_variant	Intron 1 of 21			ENSP00000507106.1

Frequencies

GnomAD3 genomes AF: 0.654 AC: 98699 AN: 150810 Hom.: 32512 Cov.: 28

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.651

Gnomad AMR AF: 0.708

Gnomad ASJ AF: 0.714

Gnomad EAS AF: 0.772

Gnomad SAS AF: 0.613

Gnomad FIN AF: 0.598

Gnomad MID AF: 0.634

Gnomad NFE AF: 0.692

Gnomad OTH AF: 0.661

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

GnomAD4 genome AF: 0.654 AC: 98746 AN: 150930 Hom.: 32519 Cov.: 28 AF XY: 0.651 AC XY: 47943 AN XY: 73700

African (AFR) AF: 0.571 AC: 23334 AN: 40890

American (AMR) AF: 0.708 AC: 10751 AN: 15190

Ashkenazi Jewish (ASJ) AF: 0.714 AC: 2474 AN: 3466

East Asian (EAS) AF: 0.771 AC: 3947 AN: 5118

South Asian (SAS) AF: 0.613 AC: 2929 AN: 4778

European-Finnish (FIN) AF: 0.598 AC: 6182 AN: 10336

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.692 AC: 46965 AN: 67860

Other (OTH) AF: 0.662 AC: 1383 AN: 2090

Alfa AF: 0.685 Hom.: 115136

Bravo AF: 0.661

Asia WGS AF: 0.679 AC: 2355 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	6.6
DANN	Benign	0.72
PhyloP100		0.042
PromoterAI		-0.018	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs8092794; hg19: chr18-32076237;