Variant chr18-34755689-A-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

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

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.349

Variant links:

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]

DTNA links:

(HGNC:):

links:

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ACMG classification

Classification made for transcript

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 GnomAd4 at 3981 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1 linkuse as main transcript	c.-1-287A>T		intron_variant		ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6 linkuse as main transcript	c.-1-287A>T		intron_variant		5	NM_001386795.1	ENSP00000405819	P3	Q9Y4J8-17
	ENST00000596954.1 linkuse as main transcript	n.314-54T>A		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.0262

AC:

3982

AN:

152170

Hom.:

106

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.0285

AC XY:

2120

AN XY:

74466

show subpopulations

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.:

Bravo

AF:

0.0183

Asia WGS

AF:

0.00318

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 28, 2018

- -

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over