Variant 20-17600993-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_006870.4(DSTN):c.259G>A(p.Ala87Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,188 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000021 ( 0 hom. )

Consequence

DSTN
NM_006870.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 8.02

Variant links:

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]

DSTN links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DSTN	NM_006870.4 linkuse as main transcript	c.259G>A	p.Ala87Thr	missense_variant	2/4	ENST00000246069.12	NP_006861.1
DSTN	NM_001011546.2 linkuse as main transcript	c.208G>A	p.Ala70Thr	missense_variant	3/5		NP_001011546.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DSTN	ENST00000246069.12 linkuse as main transcript	c.259G>A	p.Ala87Thr	missense_variant	2/4	1	NM_006870.4	ENSP00000246069	P1	P60981-1
DSTN	ENST00000474024.5 linkuse as main transcript	c.208G>A	p.Ala70Thr	missense_variant	3/5	1		ENSP00000476975		P60981-2
DSTN	ENST00000449141.2 linkuse as main transcript	c.259G>A	p.Ala87Thr	missense_variant, NMD_transcript_variant	2/5	3		ENSP00000434355

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000206

AC:

AN:

1457188

Hom.:

Cov.:

AF XY:

0.00000414

AC XY:

AN XY:

724270

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 05, 2023

The c.259G>A (p.A87T) alteration is located in exon 2 (coding exon 2) of the DSTN gene. This alteration results from a G to A substitution at nucleotide position 259, causing the alanine (A) at amino acid position 87 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.80

BayesDel_addAF

Uncertain

0.059

BayesDel_noAF

Benign

-0.15

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Benign

0.25

T;.

Eigen

Uncertain

0.31

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.89

D;D

M_CAP

Benign

0.013

MetaRNN

Uncertain

0.61

D;D

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.82

PROVEAN

Uncertain

-2.8

D;.

REVEL

Benign

0.17

Sift

Benign

0.12

T;.

Sift4G

Benign

0.35

T;T

Polyphen

0.36

B;.

Vest4

0.67

MutPred

0.47

Gain of phosphorylation at A87 (P = 0.036);.;

MVP

0.65

MPC

1.1

ClinPred

0.97

GERP RS

5.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.36

gMVP

0.50

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over