Variant rs9944927 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001198938.2(DTNA):c.2062G>A(p.Glu688Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.22 in 1,535,714 control chromosomes in the GnomAD database, including 43,444 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 8928 hom., cov: 32)

Exomes 𝑓: 0.21 ( 34516 hom. )

Consequence

DTNA
NM_001198938.2 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 1.98

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:

DTNA (HGNC:):

DTNA links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=1.4859438E-4).

BP6

Variant 18-34890327-G-A is Benign according to our data. Variant chr18-34890327-G-A is described in ClinVar as [Benign]. Clinvar id is 137181.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr18-34890327-G-A is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.557 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1 linkuse as main transcript	c.*2593G>A		3_prime_UTR_variant	23/23	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.*2593G>A		3_prime_UTR_variant	23/23	5	NM_001386795.1	ENSP00000405819.2		Q9Y4J8-17A0A7P0TBH9

Frequencies

GnomAD3 genomes

AF:

0.297

AC:

45116

AN:

151828

Hom.:

8893

Cov.:

show subpopulations

Gnomad AFR

AF:

0.563

Gnomad AMI

AF:

0.348

Gnomad AMR

AF:

0.197

Gnomad ASJ

AF:

0.278

Gnomad EAS

AF:

0.0158

Gnomad SAS

AF:

0.204

Gnomad FIN

AF:

0.190

Gnomad MID

AF:

0.241

Gnomad NFE

AF:

0.204

Gnomad OTH

AF:

0.275

GnomAD3 exomes

AF:

0.202

AC:

27673

AN:

136942

Hom.:

3634

AF XY:

0.202

AC XY:

15041

AN XY:

74366

show subpopulations

Gnomad AFR exome

AF:

0.575

Gnomad AMR exome

AF:

0.131

Gnomad ASJ exome

AF:

0.278

Gnomad EAS exome

AF:

0.0181

Gnomad SAS exome

AF:

0.216

Gnomad FIN exome

AF:

0.177

Gnomad NFE exome

AF:

0.209

Gnomad OTH exome

AF:

0.222

GnomAD4 exome

AF:

0.212

AC:

293115

AN:

1383768

Hom.:

34516

Cov.:

AF XY:

0.211

AC XY:

144206

AN XY:

682832

show subpopulations

Gnomad4 AFR exome

AF:

0.575

Gnomad4 AMR exome

AF:

0.143

Gnomad4 ASJ exome

AF:

0.280

Gnomad4 EAS exome

AF:

0.0163

Gnomad4 SAS exome

AF:

0.218

Gnomad4 FIN exome

AF:

0.178

Gnomad4 NFE exome

AF:

0.208

Gnomad4 OTH exome

AF:

0.229

GnomAD4 genome

AF:

0.298

AC:

45218

AN:

151946

Hom.:

8928

Cov.:

AF XY:

0.292

AC XY:

21708

AN XY:

74274

show subpopulations

Gnomad4 AFR

AF:

0.563

Gnomad4 AMR

AF:

0.197

Gnomad4 ASJ

AF:

0.278

Gnomad4 EAS

AF:

0.0160

Gnomad4 SAS

AF:

0.205

Gnomad4 FIN

AF:

0.190

Gnomad4 NFE

AF:

0.204

Gnomad4 OTH

AF:

0.275

Alfa

AF:

0.222

Hom.:

8290

Bravo

AF:

0.312

TwinsUK

AF:

0.207

AC:

768

ALSPAC

AF:

0.208

AC:

802

ExAC

AF:

0.213

AC:

3406

Asia WGS

AF:

0.160

AC:

556

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Benign, criteria provided, single submitter	research	Biesecker Lab/Clinical Genomics Section, National Institutes of Health	Jun 24, 2013	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 22, 2013	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. -

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.71

CADD

Benign

DANN

Benign

0.93

FATHMM_MKL

Benign

0.20

LIST_S2

Benign

0.29

MetaRNN

Benign

0.00015

Sift4G

Uncertain

0.042

Vest4

0.088

MPC

0.36

GERP RS

4.7

gMVP

0.36

Splicing

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