Variant 18-34820818-G-T details in Genebe, Genetics Data Aggregator

Variant summary

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

The NM_001386795.1(DTNA):c.904G>T(p.Ala302Ser) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,864 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: 6.8e-7 ( 0 hom. )

Consequence

DTNA
NM_001386795.1 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 10.0

Variant links:

Genes affected

DTNA (HGNC:3057): (dystrobrevin alpha) The protein encoded by this gene belongs to the dystrobrevin subfamily of the dystrophin family. This protein is a component of the dystrophin-associated protein complex (DPC), which consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and alpha- and beta-dystrobrevin. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Mutations in this gene are associated with left ventricular noncompaction with congenital heart defects. Multiple alternatively spliced transcript variants encoding different isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

DTNA 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=0.32186228).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNA	NM_001386795.1 linkuse as main transcript	c.904G>T	p.Ala302Ser	missense_variant	9/23	ENST00000444659.6	NP_001373724.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNA	ENST00000444659.6 linkuse as main transcript	c.904G>T	p.Ala302Ser	missense_variant	9/23	5	NM_001386795.1	ENSP00000405819	P3	Q9Y4J8-17

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251446

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135892

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.28

BayesDel_addAF

Uncertain

0.023

BayesDel_noAF

Benign

-0.11

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.13

.;.;.;.;.;.;.;.;.;.;T;T;T

Eigen

Uncertain

0.51

Eigen_PC

Uncertain

0.60

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Pathogenic

0.98

D;D;D;D;D;D;D;.;D;D;D;.;D

M_CAP

Benign

0.012

MetaRNN

Benign

0.32

T;T;T;T;T;T;T;T;T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;L;L;L;L;L;L;L;L;L;L;L;.

MutationTaster

Benign

1.0

D;D;D;D;D;D;D;D;D;D;D;D;D

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.58

N;N;.;N;N;.;.;.;N;.;N;N;.

REVEL

Uncertain

0.29

Sift

Benign

0.61

T;T;.;T;T;.;.;.;T;.;T;T;.

Sift4G

Benign

0.92

T;T;T;T;T;T;T;T;T;T;T;T;T

Polyphen

1.0

D;D;.;.;.;.;D;D;D;.;D;D;.

Vest4

0.63

MutPred

0.13

Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);Gain of phosphorylation at A302 (P = 0.0168);.;

MVP

0.68

MPC

0.67

ClinPred

0.63

GERP RS

5.7

Varity_R

0.30

gMVP

0.36

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