Genetic Variant ENST00000469139.2:c.-332dupA (chr3-49468836-C-CA) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The ENST00000469139.2(DAG1):c.-332dupA variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.53 ( 9470 hom., cov: 0)

Exomes 𝑓: 0.21 ( 2 hom. )

Consequence

DAG1
ENST00000469139.2 5_prime_UTR

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0230

Publications

1 publications found

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 Gene-Disease associations (from GenCC):

autosomal recessive limb-girdle muscular dystrophy type 2P
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Genomics England PanelApp, Orphanet
muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9
Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
muscular dystrophy-dystroglycanopathy, type A
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
isolated asymptomatic elevation of creatine phosphokinase
Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

DAG1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.564 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAG1	NM_001177643.3 link	c.-336_-335insA		upstream_gene_variant			NP_001171114.2	Q14118A0A024R2W4
DAG1	XM_047447546.1 link	c.-749_-748insA		upstream_gene_variant			XP_047303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000469139.2 link	c.-332dupA		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000501165.2		Q14118A0A669KB80

Frequencies

GnomAD3 genomes

AF:

0.531

AC:

51804

AN:

97518

Hom.:

9466

Cov.:

show subpopulations

Gnomad AFR

AF:

0.439

Gnomad AMI

AF:

0.523

Gnomad AMR

AF:

0.510

Gnomad ASJ

AF:

0.653

Gnomad EAS

AF:

0.295

Gnomad SAS

AF:

0.527

Gnomad FIN

AF:

0.650

Gnomad MID

AF:

0.563

Gnomad NFE

AF:

0.570

Gnomad OTH

AF:

0.545

GnomAD4 exome

AF:

0.208

AC:

AN:

Hom.:

Cov.:

AF XY:

0.147

AC XY:

AN XY:

show subpopulations

African (AFR)

AC:

AN:

American (AMR)

AC:

AN:

Ashkenazi Jewish (ASJ)

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AC:

AN:

European-Finnish (FIN)

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.205

AC:

AN:

Other (OTH)

AF:

0.500

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.567

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.531

AC:

51829

AN:

97596

Hom.:

9470

Cov.:

AF XY:

0.536

AC XY:

25367

AN XY:

47366

show subpopulations

African (AFR)

AF:

0.439

AC:

12636

AN:

28774

American (AMR)

AF:

0.510

AC:

3805

AN:

7464

Ashkenazi Jewish (ASJ)

AF:

0.653

AC:

1808

AN:

2770

East Asian (EAS)

AF:

0.295

AC:

315

AN:

1066

South Asian (SAS)

AF:

0.528

AC:

1248

AN:

2362

European-Finnish (FIN)

AF:

0.650

AC:

5351

AN:

8228

Middle Eastern (MID)

AF:

0.550

AC:

AN:

180

European-Non Finnish (NFE)

AF:

0.570

AC:

25562

AN:

44880

Other (OTH)

AF:

0.543

AC:

712

AN:

1312

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1596

3193

4789

6386

7982

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.329

Hom.:

564

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Jul 03, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.023

Mutation Taster

=300/0

polymorphism (auto)

(source)

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

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ENST00000469139.2:c.-332dupA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over