rs8092794

Positions:

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

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001386754.1(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 NM_001386754.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0420

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
DTNA	NM_001386754.1	c.-127+2759G>A		intron_variant			NP_001373683.1
DTNA	NM_001386755.1	c.-127+2759G>A		intron_variant			NP_001373684.1
DTNA	NM_001386760.1	c.-127+2759G>A		intron_variant			NP_001373689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000598774.6	c.-127+2759G>A		intron_variant		1		ENSP00000472031.1
DTNA	ENST00000315456.10	c.-127+2759G>A		intron_variant		1		ENSP00000322519.5
DTNA	ENST00000684266.1	c.-127+2759G>A		intron_variant				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

Gnomad4 AFR AF: 0.571

Gnomad4 AMR AF: 0.708

Gnomad4 ASJ AF: 0.714

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.613

Gnomad4 FIN AF: 0.598

Gnomad4 NFE AF: 0.692

Gnomad4 OTH AF: 0.662

Alfa AF: 0.690 Hom.: 50045

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

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs8092794; hg19: chr18-32076237;