18-34755689-A-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_001386795.1(DTNA):c.-1-287A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0259 in 374,824 control chromosomes in the GnomAD database, including 253 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.026 (106 hom., cov: 33)
  • Exomes 𝑓: 0.026 (147 hom.)
• Consequence: DTNA NM_001386795.1 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.349

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=-0.83).
• BP6: Variant 18-34755689-A-T is Benign according to our data. Variant chr18-34755689-A-T is described in ClinVar as [Benign]. Clinvar id is 1258003.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0261 (3981/152288) while in subpopulation NFE AF= 0.0341 (2321/68024). AF 95% confidence interval is 0.033. There are 106 homozygotes in gnomad4. There are 2120 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 3982 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DTNA	NM_001386795.1	c.-1-287A>T		intron_variant		ENST00000444659.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNA	ENST00000444659.6	c.-1-287A>T		intron_variant		5	NM_001386795.1	P3
	ENST00000596954.1	n.314-54T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.0262 AC: 3982 AN: 152170 Hom.: 106 Cov.: 33

Gnomad AFR AF: 0.00502

Gnomad AMI AF: 0.00110

Gnomad AMR AF: 0.0183

Gnomad ASJ AF: 0.0199

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00662

Gnomad FIN AF: 0.0968

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.0341

Gnomad OTH AF: 0.0215

GnomAD4 exome AF: 0.0257 AC: 5726 AN: 222536 Hom.: 147 AF XY: 0.0242 AC XY: 2898 AN XY: 119972

Gnomad4 AFR exome AF: 0.00472

Gnomad4 AMR exome AF: 0.0133

Gnomad4 ASJ exome AF: 0.0190

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00616

Gnomad4 FIN exome AF: 0.0875

Gnomad4 NFE exome AF: 0.0311

Gnomad4 OTH exome AF: 0.0260

GnomAD4 genome AF: 0.0261 AC: 3981 AN: 152288 Hom.: 106 Cov.: 33 AF XY: 0.0285 AC XY: 2120 AN XY: 74466

Gnomad4 AFR AF: 0.00500

Gnomad4 AMR AF: 0.0183

Gnomad4 ASJ AF: 0.0199

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00642

Gnomad4 FIN AF: 0.0968

Gnomad4 NFE AF: 0.0341

Gnomad4 OTH AF: 0.0213

Alfa AF: 0.0373 Hom.: 18

Bravo AF: 0.0183

Asia WGS AF: 0.00318 AC: 11 AN: 3478

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

Jun 28, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	2.2
Dann	Benign	0.78

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: rs75850110; hg19: chr18-32335653;