Variant rs1801143 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_004393.6(DAG1):c.2256C>T(p.His752=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.298 in 1,613,778 control chromosomes in the GnomAD database, including 75,680 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.30 ( 7134 hom., cov: 32)

Exomes 𝑓: 0.30 ( 68546 hom. )

Consequence

DAG1
NM_004393.6 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8O:1

Conservation

PhyloP100: 1.80

Variant links:

Genes affected

DAG1 (HGNC:2666): (dystroglycan 1) This gene encodes dystroglycan, a central component of dystrophin-glycoprotein complex that links the extracellular matrix and the cytoskeleton in the skeletal muscle. The encoded preproprotein undergoes O- and N-glycosylation, and proteolytic processing to generate alpha and beta subunits. Certain mutations in this gene are known to cause distinct forms of muscular dystrophy. Alternative splicing results in multiple transcript variants, all encoding the same protein. [provided by RefSeq, Nov 2015]

DAG1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.53).

BP6

Variant 3-49532767-C-T is Benign according to our data. Variant chr3-49532767-C-T is described in ClinVar as [Benign]. Clinvar id is 31755.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr3-49532767-C-T is described in Lovd as [Benign]. Variant chr3-49532767-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=1.8 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.301 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAG1	NM_004393.6 linkuse as main transcript	c.2256C>T	p.His752=	synonymous_variant	3/3	ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7 linkuse as main transcript	c.2256C>T	p.His752=	synonymous_variant	3/3	1	NM_004393.6	P1

Frequencies

GnomAD3 genomes

AF:

0.295

AC:

44904

AN:

152022

Hom.:

7128

Cov.:

show subpopulations

Gnomad AFR

AF:

0.290

Gnomad AMI

AF:

0.197

Gnomad AMR

AF:

0.218

Gnomad ASJ

AF:

0.461

Gnomad EAS

AF:

0.0588

Gnomad SAS

AF:

0.225

Gnomad FIN

AF:

0.471

Gnomad MID

AF:

0.320

Gnomad NFE

AF:

0.305

Gnomad OTH

AF:

0.297

GnomAD3 exomes

AF:

0.279

AC:

69706

AN:

250230

Hom.:

11291

AF XY:

0.282

AC XY:

38153

AN XY:

135412

show subpopulations

Gnomad AFR exome

AF:

0.287

Gnomad AMR exome

AF:

0.156

Gnomad ASJ exome

AF:

0.456

Gnomad EAS exome

AF:

0.0553

Gnomad SAS exome

AF:

0.235

Gnomad FIN exome

AF:

0.465

Gnomad NFE exome

AF:

0.310

Gnomad OTH exome

AF:

0.303

GnomAD4 exome

AF:

0.298

AC:

435877

AN:

1461638

Hom.:

68546

Cov.:

AF XY:

0.297

AC XY:

215892

AN XY:

727100

show subpopulations

Gnomad4 AFR exome

AF:

0.289

Gnomad4 AMR exome

AF:

0.163

Gnomad4 ASJ exome

AF:

0.455

Gnomad4 EAS exome

AF:

0.0632

Gnomad4 SAS exome

AF:

0.242

Gnomad4 FIN exome

AF:

0.454

Gnomad4 NFE exome

AF:

0.305

Gnomad4 OTH exome

AF:

0.302

GnomAD4 genome

AF:

0.295

AC:

44933

AN:

152140

Hom.:

7134

Cov.:

AF XY:

0.298

AC XY:

22153

AN XY:

74382

show subpopulations

Gnomad4 AFR

AF:

0.290

Gnomad4 AMR

AF:

0.218

Gnomad4 ASJ

AF:

0.461

Gnomad4 EAS

AF:

0.0591

Gnomad4 SAS

AF:

0.226

Gnomad4 FIN

AF:

0.471

Gnomad4 NFE

AF:

0.305

Gnomad4 OTH

AF:

0.295

Alfa

AF:

0.309

Hom.:

4549

Bravo

AF:

0.275

Asia WGS

AF:

0.149

AC:

523

AN:

3478

EpiCase

AF:

0.314

EpiControl

AF:

0.308

ClinVar

Significance: Benign

Submissions summary: Benign:8Other:1

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 05, 2016	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. -
Benign, criteria provided, single submitter	clinical testing	Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	Oct 29, 2014	p.His752His in exon 6C of DAG1: This variant is not expected to have clinical si gnificance because it has been identified in 31% (2699/8600) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs1801143). -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genetic Services Laboratory, University of Chicago	-	Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

Autosomal recessive limb-girdle muscular dystrophy type 2P

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 30, 2021	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

Muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9;C4511963:Autosomal recessive limb-girdle muscular dystrophy type 2P

Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Feb 01, 2024

- -

not provided

Other:1

not provided, no classification provided

curation

Leiden Muscular Dystrophy (DAG1)

May 13, 2011

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

6.6

DANN

Benign

0.51

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