chr2-25390277-T-C

Position:

• chr2-25390277-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DTNB	NM_021907.5	c.1576-1916A>G		intron_variant		ENST00000406818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNB	ENST00000406818.8	c.1576-1916A>G		intron_variant		1	NM_021907.5	P4

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

Gnomad4 AFR AF: 0.365

Gnomad4 AMR AF: 0.226

Gnomad4 ASJ AF: 0.117

Gnomad4 EAS AF: 0.583

Gnomad4 SAS AF: 0.183

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.184

Gnomad4 OTH AF: 0.232

Alfa AF: 0.191 Hom.: 4043

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

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: rs7577599; hg19: chr2-25613146;