Variant rs2072994 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_020780.2(DISP3):c.1948G>A(p.Ala650Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.582 in 1,613,438 control chromosomes in the GnomAD database, including 287,725 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.47 ( 20740 hom., cov: 32)

Exomes 𝑓: 0.59 ( 266985 hom. )

Consequence

DISP3
NM_020780.2 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.522

Variant links:

Genes affected

DISP3 (HGNC:29251): (dispatched RND transporter family member 3) Involved in negative regulation of neuron differentiation; positive regulation of lipid metabolic process; and positive regulation of neural precursor cell proliferation. Located in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

DISP3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=3.6140498E-6).

BP6

Variant 1-11519413-G-A is Benign according to our data. Variant chr1-11519413-G-A is described in ClinVar as [Benign]. Clinvar id is 3060671.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.627 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DISP3	NM_020780.2 linkuse as main transcript	c.1948G>A	p.Ala650Thr	missense_variant	8/21	ENST00000294484.7	NP_065831.1	Q9P2K9-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DISP3	ENST00000294484.7 linkuse as main transcript	c.1948G>A	p.Ala650Thr	missense_variant	8/21	1	NM_020780.2	ENSP00000294484.6		Q9P2K9-1

Frequencies

GnomAD3 genomes

AF:

0.471

AC:

71608

AN:

151894

Hom.:

20735

Cov.:

show subpopulations

Gnomad AFR

AF:

0.134

Gnomad AMI

AF:

0.674

Gnomad AMR

AF:

0.623

Gnomad ASJ

AF:

0.540

Gnomad EAS

AF:

0.269

Gnomad SAS

AF:

0.384

Gnomad FIN

AF:

0.634

Gnomad MID

AF:

0.544

Gnomad NFE

AF:

0.632

Gnomad OTH

AF:

0.484

GnomAD3 exomes

AF:

0.555

AC:

138471

AN:

249316

Hom.:

42314

AF XY:

0.552

AC XY:

74741

AN XY:

135280

show subpopulations

Gnomad AFR exome

AF:

0.122

Gnomad AMR exome

AF:

0.725

Gnomad ASJ exome

AF:

0.537

Gnomad EAS exome

AF:

0.268

Gnomad SAS exome

AF:

0.407

Gnomad FIN exome

AF:

0.642

Gnomad NFE exome

AF:

0.632

Gnomad OTH exome

AF:

0.598

GnomAD4 exome

AF:

0.593

AC:

866949

AN:

1461426

Hom.:

266985

Cov.:

AF XY:

0.588

AC XY:

427632

AN XY:

727030

show subpopulations

Gnomad4 AFR exome

AF:

0.118

Gnomad4 AMR exome

AF:

0.715

Gnomad4 ASJ exome

AF:

0.539

Gnomad4 EAS exome

AF:

0.256

Gnomad4 SAS exome

AF:

0.410

Gnomad4 FIN exome

AF:

0.646

Gnomad4 NFE exome

AF:

0.630

Gnomad4 OTH exome

AF:

0.556

GnomAD4 genome

AF:

0.471

AC:

71624

AN:

152012

Hom.:

20740

Cov.:

AF XY:

0.470

AC XY:

34917

AN XY:

74304

show subpopulations

Gnomad4 AFR

AF:

0.134

Gnomad4 AMR

AF:

0.624

Gnomad4 ASJ

AF:

0.540

Gnomad4 EAS

AF:

0.269

Gnomad4 SAS

AF:

0.385

Gnomad4 FIN

AF:

0.634

Gnomad4 NFE

AF:

0.632

Gnomad4 OTH

AF:

0.483

Alfa

AF:

0.585

Hom.:

33295

Bravo

AF:

0.461

TwinsUK

AF:

0.628

AC:

2327

ALSPAC

AF:

0.605

AC:

2330

ESP6500AA

AF:

0.140

AC:

566

ESP6500EA

AF:

0.616

AC:

5141

ExAC

AF:

0.543

AC:

65682

Asia WGS

AF:

0.307

AC:

1067

AN:

3478

EpiCase

AF:

0.612

EpiControl

AF:

0.618

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

DISP3-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Oct 16, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.064

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.55

CADD

Benign

0.11

DANN

Benign

0.24

DEOGEN2

Benign

0.0071

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.3

FATHMM_MKL

Benign

0.023

LIST_S2

Benign

0.60

MetaRNN

Benign

0.0000036

MetaSVM

Benign

-0.98

PrimateAI

Benign

0.24

PROVEAN

Benign

-0.37

REVEL

Benign

0.12

Sift

Benign

0.66

Sift4G

Benign

0.83

Polyphen

0.0040

Vest4

0.0090

MPC

0.36

ClinPred

0.0052

GERP RS

-5.8

Varity_R

0.028

gMVP

0.32

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over