ENST00000469139.2:c.-321_-320delTT

Variant names:

• chr3-49468840-ATT-A
• rs1553641460
• ENST00000469139.2:c.-321_-320delTT

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The ENST00000469139.2(DAG1):​c.-321_-320delTT 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 0.00012 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAG1 ENST00000469139.2 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 0 publications found

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: Orphanet, Genomics England PanelApp, G2P
• muscular dystrophy-dystroglycanopathy (congenital with brain and eye anomalies), type A9

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
• neuromuscular disease caused by qualitative or quantitative defects of alpha-dystroglycan

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• 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

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000469139.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAG1	NM_001177643.3		c.-331_-330delTT		upstream_gene	N/A	NP_001171114.2	Q14118

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DAG1	ENST00000469139.2	TSL:4	c.-321_-320delTT		5_prime_UTR	Exon 1 of 3	ENSP00000501165.2	Q14118
	DAG1	ENST00000882459.1		c.-588_-587delTT		5_prime_UTR	Exon 1 of 5	ENSP00000552518.1
	DAG1	ENST00000936846.1		c.-373_-372delTT		5_prime_UTR	Exon 1 of 4	ENSP00000606905.1

Frequencies

GnomAD3 genomes AF: 0.000102 AC: 15 AN: 146436 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000302

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000680

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000301

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 30 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 20

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 26

Other (OTH) AF: 0.00 AC: 0 AN: 2

GnomAD4 genome AF: 0.000123 AC: 18 AN: 146518 Hom.: 0 Cov.: 0 AF XY: 0.0000984 AC XY: 7 AN XY: 71134

African (AFR) AF: 0.000377 AC: 15 AN: 39796

American (AMR) AF: 0.0000679 AC: 1 AN: 14726

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3360

East Asian (EAS) AF: 0.00 AC: 0 AN: 5002

South Asian (SAS) AF: 0.00 AC: 0 AN: 4674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9410

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 286

European-Non Finnish (NFE) AF: 0.0000301 AC: 2 AN: 66350

Other (OTH) AF: 0.00 AC: 0 AN: 2020

Alfa AF: 0.00 Hom.: 792

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.096

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

Other links and lift over

dbSNP: rs1553641460; hg19: chr3-49506273;