rs2292225

Positions:

• chr2-25432577-T-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_021907.5(DTNB):​c.1457+309A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.565 in 152,014 control chromosomes in the GnomAD database, including 25,493 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 0.56 (25493 hom., cov: 32)
• Consequence: DTNB NM_021907.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNB	NM_021907.5	c.1457+309A>C		intron_variant		ENST00000406818.8	NP_068707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNB	ENST00000406818.8	c.1457+309A>C		intron_variant		1	NM_021907.5	ENSP00000384084.3

Frequencies

GnomAD3 genomes AF: 0.565 AC: 85768 AN: 151896 Hom.: 25451 Cov.: 32

Gnomad AFR AF: 0.491

Gnomad AMI AF: 0.673

Gnomad AMR AF: 0.451

Gnomad ASJ AF: 0.556

Gnomad EAS AF: 0.0907

Gnomad SAS AF: 0.557

Gnomad FIN AF: 0.593

Gnomad MID AF: 0.617

Gnomad NFE AF: 0.666

Gnomad OTH AF: 0.570

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

GnomAD4 genome AF: 0.565 AC: 85865 AN: 152014 Hom.: 25493 Cov.: 32 AF XY: 0.555 AC XY: 41240 AN XY: 74288

Gnomad4 AFR AF: 0.492

Gnomad4 AMR AF: 0.451

Gnomad4 ASJ AF: 0.556

Gnomad4 EAS AF: 0.0907

Gnomad4 SAS AF: 0.559

Gnomad4 FIN AF: 0.593

Gnomad4 NFE AF: 0.666

Gnomad4 OTH AF: 0.572

Alfa AF: 0.635 Hom.: 43225

Bravo AF: 0.546

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.32

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: rs2292225; hg19: chr2-25655446;