2-25410373-T-C

Position:

• chr2-25410373-T-C

Variant summary

Our verdict is Benign. Variant got -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

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

Verdict is Benign. Variant got -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/exons	MANE	UniProt
DTNB	NM_021907.5	c.1575+9142A>G		intron_variant		ENST00000406818.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DTNB	ENST00000406818.8	c.1575+9142A>G		intron_variant		1	NM_021907.5	P4

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

Gnomad4 AFR AF: 0.764

Gnomad4 AMR AF: 0.359

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.604

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.421

Gnomad4 NFE AF: 0.304

Gnomad4 OTH AF: 0.393

Alfa AF: 0.331 Hom.: 9470

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

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: rs10180663; hg19: chr2-25633242;