dbSNP rs369872091: DAG1:p.Arg454Gly (chr3-49531871-C-G) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_004393.6(DAG1):c.1360C>G(p.Arg454Gly) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

DAG1
NM_004393.6 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.59

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.28864866).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DAG1	NM_004393.6 link	c.1360C>G	p.Arg454Gly	missense_variant	Exon 3 of 3	ENST00000308775.7	NP_004384.5	Q14118A0A024R2W4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DAG1	ENST00000308775.7 link	c.1360C>G	p.Arg454Gly	missense_variant	Exon 3 of 3	1	NM_004393.6	ENSP00000312435.2		Q14118

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000796

AC:

AN:

251362

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135868

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000880

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461892

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727246

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Benign

-0.22

BayesDel_noAF

Benign

-0.38

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.50

D;D;D;D;D;D

Eigen

Uncertain

0.32

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.81

T;.;.;.;.;.

M_CAP

Benign

0.019

MetaRNN

Benign

0.29

T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L;L;L;L;L

PrimateAI

Uncertain

0.50

PROVEAN

Benign

-1.9

N;N;N;N;N;N

REVEL

Benign

0.090

Sift

Benign

0.086

T;T;T;T;T;T

Sift4G

Uncertain

0.041

D;D;D;D;D;D

Polyphen

0.83

P;P;P;P;P;P

Vest4

0.20

MutPred

0.42

Gain of glycosylation at T455 (P = 0.0133);Gain of glycosylation at T455 (P = 0.0133);Gain of glycosylation at T455 (P = 0.0133);Gain of glycosylation at T455 (P = 0.0133);Gain of glycosylation at T455 (P = 0.0133);Gain of glycosylation at T455 (P = 0.0133);

MVP

0.46

MPC

0.45

ClinPred

0.40

GERP RS

4.8

Varity_R

0.25

gMVP

0.58

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over