chr2-25664689-A-G

Variant names:

• chr2-25664689-A-G
• rs11684202
• NM_021907.5:c.-2+8697T>C

Variant summary

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

The NM_021907.5(DTNB):​c.-2+8697T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.282 in 152,052 control chromosomes in the GnomAD database, including 6,921 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 0.28 (6921 hom., cov: 32)
• Consequence: DTNB NM_021907.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.601
• Publications: 17 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=-0.82).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.375 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.-2+8697T>C		intron	N/A	NP_068707.1
	DTNB	NM_001320936.2		c.-2+8697T>C		intron	N/A	NP_001307865.1
	DTNB	NM_001256303.2		c.-2+8697T>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.-2+8697T>C		intron	N/A	ENSP00000384084.3
	DTNB	ENST00000407661.7	TSL:1	c.-2+8697T>C		intron	N/A	ENSP00000385193.3
	DTNB	ENST00000407038.7	TSL:1	c.-2+8697T>C		intron	N/A	ENSP00000384767.3

Frequencies

GnomAD3 genomes AF: 0.282 AC: 42820 AN: 151934 Hom.: 6926 Cov.: 32

Gnomad AFR AF: 0.136

Gnomad AMI AF: 0.365

Gnomad AMR AF: 0.256

Gnomad ASJ AF: 0.352

Gnomad EAS AF: 0.196

Gnomad SAS AF: 0.298

Gnomad FIN AF: 0.268

Gnomad MID AF: 0.291

Gnomad NFE AF: 0.379

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.282 AC: 42818 AN: 152052 Hom.: 6921 Cov.: 32 AF XY: 0.276 AC XY: 20504 AN XY: 74318

African (AFR) AF: 0.136 AC: 5654 AN: 41482

American (AMR) AF: 0.256 AC: 3908 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.352 AC: 1223 AN: 3470

East Asian (EAS) AF: 0.197 AC: 1016 AN: 5166

South Asian (SAS) AF: 0.298 AC: 1436 AN: 4816

European-Finnish (FIN) AF: 0.268 AC: 2828 AN: 10556

Middle Eastern (MID) AF: 0.265 AC: 78 AN: 294

European-Non Finnish (NFE) AF: 0.379 AC: 25772 AN: 67976

Other (OTH) AF: 0.271 AC: 571 AN: 2110

Alfa AF: 0.343 Hom.: 31770

Bravo AF: 0.275

Asia WGS AF: 0.238 AC: 830 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	4.9
DANN	Benign	0.73
PhyloP100		0.60
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: rs11684202; hg19: chr2-25887558;