chr18-34493576-G-A

Position:

• chr18-34493576-G-A

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000598774.6(DTNA):​c.-127+62G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.106 in 151,202 control chromosomes in the GnomAD database, including 1,101 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.11 (1100 hom., cov: 30)
  • Exomes 𝑓: 0.085 (1 hom.)
• Consequence: DTNA ENST00000598774.6 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0630

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.57).
• BP6: Variant 18-34493576-G-A is Benign according to our data. Variant chr18-34493576-G-A is described in ClinVar as [Benign]. Clinvar id is 1291505.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.185 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001198945.2	c.-127+62G>A		intron_variant			NP_001185874.1
DTNA	NM_001386754.1	c.-127+62G>A		intron_variant			NP_001373683.1
DTNA	NM_001386755.1	c.-127+62G>A		intron_variant			NP_001373684.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000315456.10	c.-127+62G>A		intron_variant		1		ENSP00000322519	A1
DTNA	ENST00000598774.6	c.-127+62G>A		intron_variant		1		ENSP00000472031	A1
DTNA	ENST00000283365.14	c.-2+62G>A		intron_variant		5		ENSP00000283365	A1

Frequencies

GnomAD3 genomes AF: 0.106 AC: 15970 AN: 150860 Hom.: 1100 Cov.: 30

Gnomad AFR AF: 0.0437

Gnomad AMI AF: 0.278

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.0892

Gnomad EAS AF: 0.195

Gnomad SAS AF: 0.146

Gnomad FIN AF: 0.199

Gnomad MID AF: 0.0877

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.0894

GnomAD4 exome AF: 0.0855 AC: 20 AN: 234 Hom.: 1 AF XY: 0.0663 AC XY: 11 AN XY: 166

Gnomad4 AFR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.167

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.0810

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.106 AC: 15974 AN: 150968 Hom.: 1100 Cov.: 30 AF XY: 0.112 AC XY: 8283 AN XY: 73700

Gnomad4 AFR AF: 0.0438

Gnomad4 AMR AF: 0.165

Gnomad4 ASJ AF: 0.0892

Gnomad4 EAS AF: 0.196

Gnomad4 SAS AF: 0.145

Gnomad4 FIN AF: 0.199

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.0885

Alfa AF: 0.0544 Hom.: 68

Bravo AF: 0.100

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	May 06, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.57
CADD	Benign	7.8
DANN	Benign	0.96
RBP_binding_hub_radar		0.77
RBP_regulation_power_radar		3.1

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs112193831; hg19: chr18-32073540;