NM_021907.5:c.1258-2380T>G

Variant names:

• chr2-25436375-A-C
• rs6746082
• NM_021907.5:c.1258-2380T>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.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
• Publications: 26 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]

LOC124900608 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_021907.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNB	NM_021907.5	MANE Select	c.1258-2380T>G		intron	N/A	NP_068707.1
	DTNB	NM_001320936.2		c.1258-2380T>G		intron	N/A	NP_001307865.1
	DTNB	NM_001256303.2		c.1258-2380T>G		intron	N/A	NP_001243232.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DTNB	ENST00000406818.8	TSL:1 MANE Select	c.1258-2380T>G		intron	N/A	ENSP00000384084.3
	DTNB	ENST00000407661.7	TSL:1	c.1258-2380T>G		intron	N/A	ENSP00000385193.3
	DTNB	ENST00000407038.7	TSL:1	c.1168-2380T>G		intron	N/A	ENSP00000384767.3

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

African (AFR) AF: 0.460 AC: 19010 AN: 41310

American (AMR) AF: 0.242 AC: 3695 AN: 15248

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 557 AN: 3468

East Asian (EAS) AF: 0.629 AC: 3238 AN: 5146

South Asian (SAS) AF: 0.224 AC: 1077 AN: 4808

European-Finnish (FIN) AF: 0.257 AC: 2693 AN: 10480

Middle Eastern (MID) AF: 0.214 AC: 63 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14319 AN: 67924

Other (OTH) AF: 0.252 AC: 530 AN: 2100

Alfa AF: 0.237 Hom.: 22721

Bravo AF: 0.314

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.6
DANN	Benign	0.71
PhyloP100		1.6
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: rs6746082; hg19: chr2-25659244;