3-49468866-C-T

Variant names:

• chr3-49468866-C-T
• rs6797164
• ENST00000469139.2:c.-306C>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000469139.2(DAG1):​c.-306C>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.976 in 151,002 control chromosomes in the GnomAD database, including 72,062 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.98 (72042 hom., cov: 25)
  • Exomes 𝑓: 1.0 (20 hom.)
• Consequence: DAG1 ENST00000469139.2 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.0820
• Publications: 2 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.03).
• BP6: Variant 3-49468866-C-T is Benign according to our data. Variant chr3-49468866-C-T is described in ClinVar as Benign. ClinVar VariationId is 1227418.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.993 is higher than 0.05.

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.-306C>T		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.-306C>T		5_prime_UTR	Exon 1 of 3	ENSP00000501165.2	Q14118
	DAG1	ENST00000882459.1		c.-573C>T		5_prime_UTR	Exon 1 of 5	ENSP00000552518.1
	DAG1	ENST00000936846.1		c.-358C>T		5_prime_UTR	Exon 1 of 4	ENSP00000606905.1

Frequencies

GnomAD3 genomes AF: 0.976 AC: 147253 AN: 150846 Hom.: 71988 Cov.: 25

Gnomad AFR AF: 0.916

Gnomad AMI AF: 1.00

Gnomad AMR AF: 0.992

Gnomad ASJ AF: 1.00

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.999

Gnomad FIN AF: 1.00

Gnomad MID AF: 1.00

Gnomad NFE AF: 1.00

Gnomad OTH AF: 0.986

GnomAD4 exome AF: 1.00 AC: 40 AN: 40 Hom.: 20 Cov.: 0 AF XY: 1.00 AC XY: 36 AN XY: 36

African (AFR) AF: 1.00 AC: 2 AN: 2

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 1.00 AC: 2 AN: 2

South Asian (SAS) AF: 1.00 AC: 4 AN: 4

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

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 1.00 AC: 30 AN: 30

Other (OTH) AF: 1.00 AC: 2 AN: 2

GnomAD4 genome AF: 0.976 AC: 147365 AN: 150962 Hom.: 72042 Cov.: 25 AF XY: 0.976 AC XY: 71877 AN XY: 73628

African (AFR) AF: 0.916 AC: 37545 AN: 40976

American (AMR) AF: 0.992 AC: 15041 AN: 15158

Ashkenazi Jewish (ASJ) AF: 1.00 AC: 3468 AN: 3468

East Asian (EAS) AF: 1.00 AC: 5120 AN: 5120

South Asian (SAS) AF: 0.999 AC: 4762 AN: 4766

European-Finnish (FIN) AF: 1.00 AC: 10248 AN: 10248

Middle Eastern (MID) AF: 1.00 AC: 294 AN: 294

European-Non Finnish (NFE) AF: 1.00 AC: 67913 AN: 67930

Other (OTH) AF: 0.987 AC: 2064 AN: 2092

Alfa AF: 0.984 Hom.: 9530

Bravo AF: 0.973

Asia WGS AF: 0.995 AC: 3461 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	1.0
DANN	Benign	0.42
PhyloP100		-0.082
PromoterAI		0.019	Neutral
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: rs6797164; hg19: chr3-49506299;