18-34710675-A-AGT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001386795.1(DTNA):c.-2+255_-2+256dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0299 in 147,878 control chromosomes in the GnomAD database, including 101 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.030 (101 hom., cov: 26)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.161

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-A-AGT is Benign according to our data. Variant chr18-34710675-A-AGT is described in ClinVar as [Benign]. Clinvar id is 1284129.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.056 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1	c.-2+255_-2+256dup		intron_variant		ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.-2+255_-2+256dup		intron_variant		5	NM_001386795.1	P3

Frequencies

GnomAD3 genomes AF: 0.0298 AC: 4402 AN: 147794 Hom.: 101 Cov.: 26

Gnomad AFR AF: 0.0578

Gnomad AMI AF: 0.0200

Gnomad AMR AF: 0.0136

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.0307

Gnomad SAS AF: 0.0184

Gnomad FIN AF: 0.0541

Gnomad MID AF: 0.0194

Gnomad NFE AF: 0.0143

Gnomad OTH AF: 0.0239

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

GnomAD4 genome AF: 0.0299 AC: 4418 AN: 147878 Hom.: 101 Cov.: 26 AF XY: 0.0310 AC XY: 2234 AN XY: 72084

Gnomad4 AFR AF: 0.0580

Gnomad4 AMR AF: 0.0136

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.0308

Gnomad4 SAS AF: 0.0184

Gnomad4 FIN AF: 0.0541

Gnomad4 NFE AF: 0.0143

Gnomad4 OTH AF: 0.0236

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

Feb 03, 2020

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Computational scores

Source: dbNSFP v4.3

Splicing

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;