3-49488610-TA-T

Variant summary

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

The NM_004393.6(DAG1):c.-117+18178del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00652 in 149,550 control chromosomes in the GnomAD database, including 4 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0065 (4 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: DAG1 NM_004393.6 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.944

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 3-49488610-TA-T is Benign according to our data. Variant chr3-49488610-TA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1202821.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DAG1	NM_004393.6	c.-117+18178del		intron_variant		ENST00000308775.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DAG1	ENST00000308775.7	c.-117+18178del		intron_variant		1	NM_004393.6	P1

Frequencies

GnomAD3 genomes AF: 0.00650 AC: 971 AN: 149480 Hom.: 4 Cov.: 29

Gnomad AFR AF: 0.00152

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00875

Gnomad ASJ AF: 0.0273

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000211

Gnomad FIN AF: 0.00845

Gnomad MID AF: 0.0195

Gnomad NFE AF: 0.00847

Gnomad OTH AF: 0.0122

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 2 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 2

Gnomad4 NFE exome AF: 0.00

GnomAD4 genome AF: 0.00652 AC: 975 AN: 149550 Hom.: 4 Cov.: 29 AF XY: 0.00630 AC XY: 459 AN XY: 72912

Gnomad4 AFR AF: 0.00154

Gnomad4 AMR AF: 0.00874

Gnomad4 ASJ AF: 0.0273

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.000423

Gnomad4 FIN AF: 0.00845

Gnomad4 NFE AF: 0.00847

Gnomad4 OTH AF: 0.0121

Alfa AF: 0.00371 Hom.: 0

Asia WGS AF: 0.0760 AC: 263 AN: 3472

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 03, 2018

- -

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: rs200848559; hg19: chr3-49526043;