rs17791782

Positions:

• chr20-17585424-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_006870.4(DSTN):​c.3+15213A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0636 in 152,284 control chromosomes in the GnomAD database, including 375 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 0.064 (375 hom., cov: 32)
• Consequence: DSTN NM_006870.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.695

Genes affected

DSTN (HGNC:15750): (destrin, actin depolymerizing factor) The product of this gene belongs to the actin-binding proteins ADF family. This family of proteins is responsible for enhancing the turnover rate of actin in vivo. This gene encodes the actin depolymerizing protein that severs actin filaments (F-actin) and binds to actin monomers (G-actin). Two transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0854 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTN	NM_006870.4	c.3+15213A>T		intron_variant		ENST00000246069.12	NP_006861.1
DSTN	NM_001011546.2	c.-180-6508A>T		intron_variant			NP_001011546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSTN	ENST00000246069.12	c.3+15213A>T		intron_variant		1	NM_006870.4	ENSP00000246069	P1
DSTN	ENST00000474024.5	c.-180-6508A>T		intron_variant		1		ENSP00000476975
DSTN	ENST00000449141.2	c.3+15213A>T		intron_variant, NMD_transcript_variant		3		ENSP00000434355

Frequencies

GnomAD3 genomes AF: 0.0637 AC: 9690 AN: 152166 Hom.: 375 Cov.: 32

Gnomad AFR AF: 0.0340

Gnomad AMI AF: 0.0822

Gnomad AMR AF: 0.0580

Gnomad ASJ AF: 0.0519

Gnomad EAS AF: 0.00327

Gnomad SAS AF: 0.0315

Gnomad FIN AF: 0.0814

Gnomad MID AF: 0.0411

Gnomad NFE AF: 0.0873

Gnomad OTH AF: 0.0760

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

GnomAD4 genome AF: 0.0636 AC: 9686 AN: 152284 Hom.: 375 Cov.: 32 AF XY: 0.0619 AC XY: 4607 AN XY: 74482

Gnomad4 AFR AF: 0.0339

Gnomad4 AMR AF: 0.0578

Gnomad4 ASJ AF: 0.0519

Gnomad4 EAS AF: 0.00309

Gnomad4 SAS AF: 0.0309

Gnomad4 FIN AF: 0.0814

Gnomad4 NFE AF: 0.0873

Gnomad4 OTH AF: 0.0762

Alfa AF: 0.0841 Hom.: 70

Bravo AF: 0.0616

Asia WGS AF: 0.0360 AC: 123 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.63
DANN	Benign	0.88

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: rs17791782; hg19: chr20-17566069;