18-34755951-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001386795.1(DTNA):c.-1-25A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0748 in 1,605,282 control chromosomes in the GnomAD database, including 5,033 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.077 (516 hom., cov: 33)
  • Exomes 𝑓: 0.075 (4517 hom.)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.369

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 18-34755951-A-G is Benign according to our data. Variant chr18-34755951-A-G is described in ClinVar as [Benign]. Clinvar id is 192362.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0973 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1	c.-1-25A>G		intron_variant		ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.-1-25A>G		intron_variant		5	NM_001386795.1	P3
	ENST00000596954.1	n.314-316T>C		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0767 AC: 11668 AN: 152162 Hom.: 514 Cov.: 33

Gnomad AFR AF: 0.0998

Gnomad AMI AF: 0.145

Gnomad AMR AF: 0.0436

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.000577

Gnomad SAS AF: 0.0108

Gnomad FIN AF: 0.0715

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0822

Gnomad OTH AF: 0.0616

GnomAD3 exomes AF: 0.0603 AC: 14983 AN: 248488 Hom.: 610 AF XY: 0.0592 AC XY: 7949 AN XY: 134374

Gnomad AFR exome AF: 0.102

Gnomad AMR exome AF: 0.0351

Gnomad ASJ exome AF: 0.0474

Gnomad EAS exome AF: 0.000602

Gnomad SAS exome AF: 0.0123

Gnomad FIN exome AF: 0.0771

Gnomad NFE exome AF: 0.0828

Gnomad OTH exome AF: 0.0594

GnomAD4 exome AF: 0.0746 AC: 108375 AN: 1453002 Hom.: 4517 Cov.: 29 AF XY: 0.0726 AC XY: 52479 AN XY: 723238

Gnomad4 AFR exome AF: 0.104

Gnomad4 AMR exome AF: 0.0361

Gnomad4 ASJ exome AF: 0.0502

Gnomad4 EAS exome AF: 0.000532

Gnomad4 SAS exome AF: 0.0126

Gnomad4 FIN exome AF: 0.0749

Gnomad4 NFE exome AF: 0.0837

Gnomad4 OTH exome AF: 0.0711

GnomAD4 genome AF: 0.0767 AC: 11685 AN: 152280 Hom.: 516 Cov.: 33 AF XY: 0.0745 AC XY: 5546 AN XY: 74462

Gnomad4 AFR AF: 0.0998

Gnomad4 AMR AF: 0.0436

Gnomad4 ASJ AF: 0.0553

Gnomad4 EAS AF: 0.000579

Gnomad4 SAS AF: 0.0108

Gnomad4 FIN AF: 0.0715

Gnomad4 NFE AF: 0.0822

Gnomad4 OTH AF: 0.0624

Alfa AF: 0.0557 Hom.: 89

Bravo AF: 0.0759

Asia WGS AF: 0.0170 AC: 58 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 08, 2014

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.20
Dann	Benign	0.29
La Branchor		0.35

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs6650658; hg19: chr18-32335915;