Variant 2-25388233-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_ModerateBP6_Very_StrongBP7BS2

The NM_021907.5(DTNB):c.1704C>T(p.Val568Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00508 in 1,596,486 control chromosomes in the GnomAD database, including 28 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0027 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0053 ( 27 hom. )

Consequence

DTNB
NM_021907.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.631

Variant links:

Genes affected

DTNB (HGNC:3058): (dystrobrevin beta) This gene encodes dystrobrevin beta, a component of the dystrophin-associated protein complex (DPC). The DPC consists of dystrophin and several integral and peripheral membrane proteins, including dystroglycans, sarcoglycans, syntrophins and dystrobrevin alpha and beta. The DPC localizes to the sarcolemma and its disruption is associated with various forms of muscular dystrophy. Dystrobrevin beta is thought to interact with syntrophin and the DP71 short form of dystrophin. [provided by RefSeq, Mar 2016]

DTNB links:

DTNB (HGNC:):

DTNB links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -15 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.39).

BP6

Variant 2-25388233-G-A is Benign according to our data. Variant chr2-25388233-G-A is described in ClinVar as [Benign]. Clinvar id is 734090.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.631 with no splicing effect.

BS2

High Homozygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNB	NM_021907.5 linkuse as main transcript	c.1704C>T	p.Val568Val	synonymous_variant	17/21	ENST00000406818.8	NP_068707.1	O60941-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNB	ENST00000406818.8 linkuse as main transcript	c.1704C>T	p.Val568Val	synonymous_variant	17/21	1	NM_021907.5	ENSP00000384084.3		O60941-1

Frequencies

GnomAD3 genomes

AF:

0.00271

AC:

412

AN:

152226

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00170

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00151

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00478

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00284

AC:

621

AN:

218564

Hom.:

AF XY:

0.00284

AC XY:

337

AN XY:

118542

show subpopulations

Gnomad AFR exome

AF:

0.000778

Gnomad AMR exome

AF:

0.00139

Gnomad ASJ exome

AF:

0.000317

Gnomad EAS exome

AF:

0.0000628

Gnomad SAS exome

AF:

0.000801

Gnomad FIN exome

AF:

0.00150

Gnomad NFE exome

AF:

0.00500

Gnomad OTH exome

AF:

0.00455

GnomAD4 exome

AF:

0.00533

AC:

7695

AN:

1444142

Hom.:

Cov.:

AF XY:

0.00520

AC XY:

3727

AN XY:

716908

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.00157

Gnomad4 ASJ exome

AF:

0.000233

Gnomad4 EAS exome

AF:

0.0000512

Gnomad4 SAS exome

AF:

0.000730

Gnomad4 FIN exome

AF:

0.00180

Gnomad4 NFE exome

AF:

0.00643

Gnomad4 OTH exome

AF:

0.00559

GnomAD4 genome

AF:

0.00270

AC:

412

AN:

152344

Hom.:

Cov.:

AF XY:

0.00227

AC XY:

169

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00170

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00151

Gnomad4 NFE

AF:

0.00478

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00246

Hom.:

Bravo

AF:

0.00283

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Dec 31, 2019	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.39

CADD

Benign

2.5

DANN

Benign

0.64

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over