3-49510406-C-CT

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_Moderate BS2

The NM_004393.6(DAG1):c.-116-4dup variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0083 in 921,352 control chromosomes in the GnomAD database, including 34 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0054 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0089 (32 hom.)
• Consequence: DAG1 NM_004393.6 splice_polypyrimidine_tract, intron
• Clinical Significance: Benign criteria provided, single submitter B:3
• Conservation: PhyloP100: 0.648

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 Likely_benign. Variant got -6 ACMG points.

• BP6: Variant 3-49510406-C-CT is Benign according to our data. Variant chr3-49510406-C-CT is described in ClinVar as [Benign]. Clinvar id is 420471.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAG1	NM_004393.6	c.-116-4dup		splice_polypyrimidine_tract_variant, intron_variant		ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.-116-4dup		splice_polypyrimidine_tract_variant, intron_variant		1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.00537 AC: 812 AN: 151318 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00214

Gnomad AMI AF: 0.00330

Gnomad AMR AF: 0.00620

Gnomad ASJ AF: 0.00924

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00105

Gnomad FIN AF: 0.00238

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00812

Gnomad OTH AF: 0.00674

GnomAD4 exome AF: 0.00887 AC: 6831 AN: 769918 Hom.: 32 Cov.: 11 AF XY: 0.00850 AC XY: 3464 AN XY: 407358

Gnomad4 AFR exome AF: 0.00285

Gnomad4 AMR exome AF: 0.00555

Gnomad4 ASJ exome AF: 0.0104

Gnomad4 EAS exome AF: 0.000221

Gnomad4 SAS exome AF: 0.00177

Gnomad4 FIN exome AF: 0.00448

Gnomad4 NFE exome AF: 0.0112

Gnomad4 OTH exome AF: 0.00944

GnomAD4 genome AF: 0.00536 AC: 812 AN: 151434 Hom.: 2 Cov.: 32 AF XY: 0.00506 AC XY: 374 AN XY: 73960

Gnomad4 AFR AF: 0.00213

Gnomad4 AMR AF: 0.00619

Gnomad4 ASJ AF: 0.00924

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00105

Gnomad4 FIN AF: 0.00238

Gnomad4 NFE AF: 0.00813

Gnomad4 OTH AF: 0.00667

Bravo AF: 0.00569

Asia WGS AF: 0.00260 AC: 9 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 29, 2019	- -
Likely benign, no assertion criteria provided	clinical testing	Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	-	- -
Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -

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: rs200455639; hg19: chr3-49547839;