3-49468836-C-CA

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000469139.2(DAG1):c.-332dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.53 (9470 hom., cov: 0)
  • Exomes 𝑓: 0.21 (2 hom.)
• Consequence: DAG1 ENST00000469139.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0230

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 3-49468836-C-CA is Benign according to our data. Variant chr3-49468836-C-CA is described in ClinVar as [Benign]. Clinvar id is 1232166.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000469139.2	c.-332dup		5_prime_UTR_variant	1/3	4		P1

Frequencies

GnomAD3 genomes AF: 0.531 AC: 51804 AN: 97518 Hom.: 9466 Cov.: 0

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: 10 AN: 48 Hom.: 2 Cov.: 0 AF XY: 0.147 AC XY: 5 AN XY: 34

Gnomad4 EAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.205

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.531 AC: 51829 AN: 97596 Hom.: 9470 Cov.: 0 AF XY: 0.536 AC XY: 25367 AN XY: 47366

Gnomad4 AFR AF: 0.439

Gnomad4 AMR AF: 0.510

Gnomad4 ASJ AF: 0.653

Gnomad4 EAS AF: 0.295

Gnomad4 SAS AF: 0.528

Gnomad4 FIN AF: 0.650

Gnomad4 NFE AF: 0.570

Gnomad4 OTH AF: 0.543

Alfa AF: 0.329 Hom.: 564

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

Jul 03, 2018

- -

Computational scores

Source: dbNSFP v4.3

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: rs71080520; hg19: chr3-49506269;