3-49468840-A-AT

Variant names:

• chr3-49468840-A-AT
• rs1553641460
• ENST00000469139.2:c.-320dupT

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The ENST00000469139.2(DAG1):​c.-320dupT 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 0.62 (28398 hom., cov: 0)
  • Exomes 𝑓: 0.33 (1 hom.)
• Consequence: DAG1 ENST00000469139.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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: 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

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP6: Variant 3-49468840-A-AT is Benign according to our data. Variant chr3-49468840-A-AT is described in ClinVar as [Benign]. Clinvar id is 1269929.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.911 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAG1	NM_001177643.3	c.-332_-331insT		upstream_gene_variant			NP_001171114.2
DAG1	XM_047447546.1	c.-745_-744insT		upstream_gene_variant			XP_047303502.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000469139.2	c.-320dupT		5_prime_UTR_variant	Exon 1 of 3	4		ENSP00000501165.2

Frequencies

GnomAD3 genomes AF: 0.623 AC: 91011 AN: 146200 Hom.: 28387 Cov.: 0

Gnomad AFR AF: 0.571

Gnomad AMI AF: 0.680

Gnomad AMR AF: 0.736

Gnomad ASJ AF: 0.482

Gnomad EAS AF: 0.934

Gnomad SAS AF: 0.733

Gnomad FIN AF: 0.467

Gnomad MID AF: 0.667

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.629

GnomAD4 exome AF: 0.333 AC: 10 AN: 30 Hom.: 1 Cov.: 0 AF XY: 0.400 AC XY: 8 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: 0.500 AC: 1 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: 0.346 AC: 9 AN: 26

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

GnomAD4 genome AF: 0.622 AC: 91055 AN: 146282 Hom.: 28398 Cov.: 0 AF XY: 0.621 AC XY: 44089 AN XY: 71006

African (AFR) AF: 0.571 AC: 22706 AN: 39734

American (AMR) AF: 0.736 AC: 10828 AN: 14708

Ashkenazi Jewish (ASJ) AF: 0.482 AC: 1616 AN: 3354

East Asian (EAS) AF: 0.933 AC: 4663 AN: 4996

South Asian (SAS) AF: 0.732 AC: 3415 AN: 4666

European-Finnish (FIN) AF: 0.467 AC: 4378 AN: 9382

Middle Eastern (MID) AF: 0.664 AC: 190 AN: 286

European-Non Finnish (NFE) AF: 0.625 AC: 41375 AN: 66244

Other (OTH) AF: 0.632 AC: 1276 AN: 2018

Alfa AF: 0.416 Hom.: 792

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Nov 19, 2019

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.096
Mutation Taster		=300/0	polymorphism (auto)

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;