2-25390277-T-C

Variant names:

• chr2-25390277-T-C
• rs7577599
• NM_021907.5:c.1576-1916A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021907.5(DTNB):​c.1576-1916A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.258 in 152,038 control chromosomes in the GnomAD database, including 5,888 homozygotes. 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: 𝑓 0.26 (5888 hom., cov: 32)
• Consequence: DTNB NM_021907.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.13
• Publications: 19 publications found

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]

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.566 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNB	NM_021907.5	c.1576-1916A>G		intron_variant	Intron 16 of 20	ENST00000406818.8	NP_068707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNB	ENST00000406818.8	c.1576-1916A>G		intron_variant	Intron 16 of 20	1	NM_021907.5	ENSP00000384084.3

Frequencies

GnomAD3 genomes AF: 0.258 AC: 39193 AN: 151920 Hom.: 5887 Cov.: 32

Gnomad AFR AF: 0.366

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.226

Gnomad ASJ AF: 0.117

Gnomad EAS AF: 0.583

Gnomad SAS AF: 0.183

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.190

Gnomad NFE AF: 0.184

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.258 AC: 39200 AN: 152038 Hom.: 5888 Cov.: 32 AF XY: 0.262 AC XY: 19440 AN XY: 74318

African (AFR) AF: 0.365 AC: 15133 AN: 41446

American (AMR) AF: 0.226 AC: 3449 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.117 AC: 406 AN: 3468

East Asian (EAS) AF: 0.583 AC: 3012 AN: 5166

South Asian (SAS) AF: 0.183 AC: 881 AN: 4826

European-Finnish (FIN) AF: 0.287 AC: 3030 AN: 10546

Middle Eastern (MID) AF: 0.180 AC: 53 AN: 294

European-Non Finnish (NFE) AF: 0.184 AC: 12518 AN: 67990

Other (OTH) AF: 0.232 AC: 489 AN: 2112

Alfa AF: 0.211 Hom.: 12289

Bravo AF: 0.267

Asia WGS AF: 0.342 AC: 1187 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.1
DANN	Benign	0.54
PhyloP100		-1.1
Mutation Taster		=100/0	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: rs7577599; hg19: chr2-25613146;