rs2292225

Variant names:

• chr2-25432577-T-G
• rs2292225
• NM_021907.5:c.1457+309A>C

Variant summary

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

The ENST00000406818.8(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 ENST00000406818.8 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.322
• Publications: 7 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=-0.87).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.661 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000406818.8. 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.1457+309A>C		intron	N/A	NP_068707.1
	DTNB	NM_001320936.2		c.1457+309A>C		intron	N/A	NP_001307865.1
	DTNB	NM_001256303.2		c.1457+309A>C		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.1457+309A>C		intron	N/A	ENSP00000384084.3
	DTNB	ENST00000407661.7	TSL:1	c.1457+309A>C		intron	N/A	ENSP00000385193.3
	DTNB	ENST00000407038.7	TSL:1	c.1367+309A>C		intron	N/A	ENSP00000384767.3

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

African (AFR) AF: 0.492 AC: 20381 AN: 41432

American (AMR) AF: 0.451 AC: 6883 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.556 AC: 1922 AN: 3458

East Asian (EAS) AF: 0.0907 AC: 469 AN: 5170

South Asian (SAS) AF: 0.559 AC: 2689 AN: 4814

European-Finnish (FIN) AF: 0.593 AC: 6265 AN: 10564

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.666 AC: 45257 AN: 67986

Other (OTH) AF: 0.572 AC: 1206 AN: 2110

Alfa AF: 0.623 Hom.: 57548

Bravo AF: 0.546

Asia WGS AF: 0.387 AC: 1348 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.64
DANN	Benign	0.32
PhyloP100		-0.32
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: rs2292225; hg19: chr2-25655446;