chr3-49534029-G-T

Variant names:

• chr3-49534029-G-T
• rs12583
• NM_004393.6:c.*830G>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004393.6(DAG1):​c.*830G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.238 in 152,586 control chromosomes in the GnomAD database, including 4,618 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as not provided (no stars).

• Frequency:
  • Genomes: 𝑓 0.24 (4604 hom., cov: 33)
  • Exomes 𝑓: 0.24 (14 hom.)
• Consequence: DAG1 NM_004393.6 3_prime_UTR
• Clinical Significance: not provided no classification provided O:1
• Conservation: PhyloP100: 2.10
• Publications: 19 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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.52).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.265 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAG1	NM_004393.6	c.*830G>T		3_prime_UTR_variant	Exon 3 of 3	ENST00000308775.7	NP_004384.5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000308775.7	c.*830G>T		3_prime_UTR_variant	Exon 3 of 3	1	NM_004393.6	ENSP00000312435.2

Frequencies

GnomAD3 genomes AF: 0.238 AC: 36121 AN: 151976 Hom.: 4591 Cov.: 33

Gnomad AFR AF: 0.269

Gnomad AMI AF: 0.269

Gnomad AMR AF: 0.192

Gnomad ASJ AF: 0.192

Gnomad EAS AF: 0.00866

Gnomad SAS AF: 0.0863

Gnomad FIN AF: 0.182

Gnomad MID AF: 0.277

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.249

GnomAD4 exome AF: 0.236 AC: 116 AN: 492 Hom.: 14 Cov.: 0 AF XY: 0.268 AC XY: 81 AN XY: 302

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.143 AC: 2 AN: 14

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AF: 0.125 AC: 1 AN: 8

European-Finnish (FIN) AF: 0.168 AC: 36 AN: 214

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.310 AC: 77 AN: 248

Other (OTH) AF: 0.00 AC: 0 AN: 8

GnomAD4 genome AF: 0.238 AC: 36165 AN: 152094 Hom.: 4604 Cov.: 33 AF XY: 0.230 AC XY: 17087 AN XY: 74352

African (AFR) AF: 0.269 AC: 11168 AN: 41470

American (AMR) AF: 0.192 AC: 2931 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.192 AC: 664 AN: 3464

East Asian (EAS) AF: 0.00849 AC: 44 AN: 5182

South Asian (SAS) AF: 0.0863 AC: 417 AN: 4830

European-Finnish (FIN) AF: 0.182 AC: 1925 AN: 10586

Middle Eastern (MID) AF: 0.284 AC: 83 AN: 292

European-Non Finnish (NFE) AF: 0.267 AC: 18169 AN: 67970

Other (OTH) AF: 0.246 AC: 520 AN: 2112

Alfa AF: 0.254 Hom.: 804

Bravo AF: 0.240

Asia WGS AF: 0.0670 AC: 234 AN: 3478

ClinVar

Significance: not provided

Submissions summary: Other:1

Revision: no classification provided

Submissions by phenotype

not provided Other:1

May 13, 2011

Leiden Muscular Dystrophy (DAG1)

Significance: not provided

Review Status: no classification provided

Collection Method: curation

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.52
CADD	Benign	14
DANN	Benign	0.80
PhyloP100		2.1
Mutation Taster		=100/0	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: rs12583; hg19: chr3-49571462;