18-34710675-A-AGTGT

Position:

• chr18-34710675-A-AGTGT

Variant summary

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

The NM_001386795.1(DTNA):​c.-2+253_-2+256dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.127 in 147,864 control chromosomes in the GnomAD database, including 1,240 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.13 (1240 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-AGTGT is Benign according to our data. Variant chr18-34710675-A-AGTGT is described in ClinVar as [Benign]. Clinvar id is 1181084.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.193 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.-2+253_-2+256dup		intron_variant		ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.-2+253_-2+256dup		intron_variant		5	NM_001386795.1	ENSP00000405819	P3

Frequencies

GnomAD3 genomes AF: 0.127 AC: 18722 AN: 147780 Hom.: 1240 Cov.: 26

Gnomad AFR AF: 0.197

Gnomad AMI AF: 0.0532

Gnomad AMR AF: 0.0918

Gnomad ASJ AF: 0.0750

Gnomad EAS AF: 0.0348

Gnomad SAS AF: 0.0988

Gnomad FIN AF: 0.142

Gnomad MID AF: 0.0935

Gnomad NFE AF: 0.102

Gnomad OTH AF: 0.117

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

GnomAD4 genome AF: 0.127 AC: 18734 AN: 147864 Hom.: 1240 Cov.: 26 AF XY: 0.128 AC XY: 9187 AN XY: 72054

Gnomad4 AFR AF: 0.197

Gnomad4 AMR AF: 0.0917

Gnomad4 ASJ AF: 0.0750

Gnomad4 EAS AF: 0.0347

Gnomad4 SAS AF: 0.0981

Gnomad4 FIN AF: 0.142

Gnomad4 NFE AF: 0.102

Gnomad4 OTH AF: 0.118

Bravo AF: 0.127

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

- -

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;