2-25436375-A-C

Position:

• chr2-25436375-A-C

Variant summary

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

The NM_021907.5(DTNB):​c.1258-2380T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.3 in 151,690 control chromosomes in the GnomAD database, including 8,112 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 0.30 (8112 hom., cov: 31)
• Consequence: DTNB NM_021907.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.60

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]

LOC124900608 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.611 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DTNB	NM_021907.5	c.1258-2380T>G		intron_variant		ENST00000406818.8	NP_068707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DTNB	ENST00000406818.8	c.1258-2380T>G		intron_variant		1	NM_021907.5	ENSP00000384084.3

Frequencies

GnomAD3 genomes AF: 0.300 AC: 45444 AN: 151572 Hom.: 8114 Cov.: 31

Gnomad AFR AF: 0.461

Gnomad AMI AF: 0.303

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.161

Gnomad EAS AF: 0.630

Gnomad SAS AF: 0.225

Gnomad FIN AF: 0.257

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.255

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

GnomAD4 genome AF: 0.300 AC: 45458 AN: 151690 Hom.: 8112 Cov.: 31 AF XY: 0.300 AC XY: 22202 AN XY: 74106

Gnomad4 AFR AF: 0.460

Gnomad4 AMR AF: 0.242

Gnomad4 ASJ AF: 0.161

Gnomad4 EAS AF: 0.629

Gnomad4 SAS AF: 0.224

Gnomad4 FIN AF: 0.257

Gnomad4 NFE AF: 0.211

Gnomad4 OTH AF: 0.252

Alfa AF: 0.216 Hom.: 8705

Bravo AF: 0.314

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.71

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: rs6746082; hg19: chr2-25659244;