2-25410373-T-C

Variant names:

• chr2-25410373-T-C
• rs10180663
• NM_021907.5:c.1575+9142A>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.1575+9142A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.456 in 151,972 control chromosomes in the GnomAD database, including 18,910 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 0.46 (18910 hom., cov: 31)
• Consequence: DTNB NM_021907.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.567
• Publications: 18 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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.757 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DTNB	NM_021907.5	c.1575+9142A>G		intron_variant	Intron 16 of 20	ENST00000406818.8	NP_068707.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DTNB	ENST00000406818.8	c.1575+9142A>G		intron_variant	Intron 16 of 20	1	NM_021907.5	ENSP00000384084.3

Frequencies

GnomAD3 genomes AF: 0.456 AC: 69226 AN: 151854 Hom.: 18863 Cov.: 31

Gnomad AFR AF: 0.763

Gnomad AMI AF: 0.432

Gnomad AMR AF: 0.359

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.604

Gnomad SAS AF: 0.306

Gnomad FIN AF: 0.421

Gnomad MID AF: 0.329

Gnomad NFE AF: 0.304

Gnomad OTH AF: 0.397

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

GnomAD4 genome AF: 0.456 AC: 69318 AN: 151972 Hom.: 18910 Cov.: 31 AF XY: 0.457 AC XY: 33898 AN XY: 74252

African (AFR) AF: 0.764 AC: 31681 AN: 41470

American (AMR) AF: 0.359 AC: 5474 AN: 15268

Ashkenazi Jewish (ASJ) AF: 0.330 AC: 1144 AN: 3468

East Asian (EAS) AF: 0.604 AC: 3116 AN: 5160

South Asian (SAS) AF: 0.305 AC: 1467 AN: 4814

European-Finnish (FIN) AF: 0.421 AC: 4438 AN: 10548

Middle Eastern (MID) AF: 0.327 AC: 96 AN: 294

European-Non Finnish (NFE) AF: 0.304 AC: 20679 AN: 67930

Other (OTH) AF: 0.393 AC: 830 AN: 2110

Alfa AF: 0.363 Hom.: 32722

Bravo AF: 0.469

Asia WGS AF: 0.454 AC: 1576 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.7
DANN	Benign	0.72
PhyloP100		-0.57
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: rs10180663; hg19: chr2-25633242;