18-34710675-AGTGTGTGTGTGT-AGTGTGTGTGTGTGTGTGT

Variant names:

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

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001386795.1(DTNA):​c.-2+251_-2+256dupGTGTGT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00135 in 147,942 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.0014 (3 hom., cov: 26)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Not reported in ClinVar
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 200 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNA	NM_001386795.1	c.-2+251_-2+256dupGTGTGT		intron_variant	Intron 1 of 22	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6	c.-2+230_-2+231insGTGTGT		intron_variant	Intron 1 of 22	5	NM_001386795.1	ENSP00000405819.2

Frequencies

GnomAD3 genomes AF: 0.00134 AC: 198 AN: 147858 Hom.: 3 Cov.: 26

Gnomad AFR AF: 0.00158

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000953

Gnomad ASJ AF: 0.000586

Gnomad EAS AF: 0.000989

Gnomad SAS AF: 0.0110

Gnomad FIN AF: 0.000510

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000782

Gnomad OTH AF: 0.00248

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

GnomAD4 genome AF: 0.00135 AC: 200 AN: 147942 Hom.: 3 Cov.: 26 AF XY: 0.00150 AC XY: 108 AN XY: 72110

Gnomad4 AFR AF: 0.00160

Gnomad4 AMR AF: 0.000952

Gnomad4 ASJ AF: 0.000586

Gnomad4 EAS AF: 0.000992

Gnomad4 SAS AF: 0.0111

Gnomad4 FIN AF: 0.000510

Gnomad4 NFE AF: 0.000782

Gnomad4 OTH AF: 0.00295

ClinVar

Not reported in ClinVar

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;