Variant chr17-18100605-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001388.5(DRG2):c.577G>A(p.Val193Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00437 in 1,614,174 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0040 ( 1 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 26 hom. )

Consequence

DRG2
NM_001388.5 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 7.89

Variant links:

Genes affected

DRG2 (HGNC:3030): (developmentally regulated GTP binding protein 2) This gene encodes a GTP-binding protein known to function in the regulation of cell growth and differentiation. Read-through transcripts containing this gene and a downstream gene have been identified, but they are not thought to encode a fusion protein. This gene is located within the Smith-Magenis syndrome region on chromosome 17. [provided by RefSeq, Jan 2012]

DRG2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0052012503).

BP6

Variant 17-18100605-G-A is Benign according to our data. Variant chr17-18100605-G-A is described in ClinVar as [Benign]. Clinvar id is 782152.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 26 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRG2	NM_001388.5 linkuse as main transcript	c.577G>A	p.Val193Ile	missense_variant	7/13	ENST00000225729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRG2	ENST00000225729.8 linkuse as main transcript	c.577G>A	p.Val193Ile	missense_variant	7/13	1	NM_001388.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00402

AC:

612

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00106

Gnomad AMI

AF:

0.00110

Gnomad AMR

AF:

0.00157

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000828

Gnomad FIN

AF:

0.0184

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00497

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.00406

AC:

1020

AN:

251360

Hom.:

AF XY:

0.00390

AC XY:

530

AN XY:

135854

show subpopulations

Gnomad AFR exome

AF:

0.000615

Gnomad AMR exome

AF:

0.00142

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000392

Gnomad FIN exome

AF:

0.0171

Gnomad NFE exome

AF:

0.00486

Gnomad OTH exome

AF:

0.00456

GnomAD4 exome

AF:

0.00441

AC:

6447

AN:

1461864

Hom.:

Cov.:

AF XY:

0.00425

AC XY:

3090

AN XY:

727232

show subpopulations

Gnomad4 AFR exome

AF:

0.000806

Gnomad4 AMR exome

AF:

0.00154

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000371

Gnomad4 FIN exome

AF:

0.0176

Gnomad4 NFE exome

AF:

0.00462

Gnomad4 OTH exome

AF:

0.00376

GnomAD4 genome

AF:

0.00401

AC:

611

AN:

152310

Hom.:

Cov.:

AF XY:

0.00423

AC XY:

315

AN XY:

74464

show subpopulations

Gnomad4 AFR

AF:

0.00106

Gnomad4 AMR

AF:

0.00157

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.0184

Gnomad4 NFE

AF:

0.00495

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.00421

Hom.:

Bravo

AF:

0.00272

TwinsUK

AF:

0.00378

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00406

AC:

493

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00349

EpiControl

AF:

0.00362

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Nov 10, 2017

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.096

BayesDel_addAF

Benign

-0.41

BayesDel_noAF

Benign

-0.36

CADD

Uncertain

DANN

Benign

0.96

DEOGEN2

Benign

0.013

T;T;T

Eigen

Benign

0.080

Eigen_PC

Benign

0.19

FATHMM_MKL

Pathogenic

0.97

LIST_S2

Pathogenic

0.98

D;D;D

MetaRNN

Benign

0.0052

T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.8

L;.;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.67

PROVEAN

Benign

-0.42

N;N;.

REVEL

Benign

0.17

Sift

Benign

0.095

T;T;.

Sift4G

Benign

0.11

T;T;T

Polyphen

0.015

B;B;.

Vest4

0.59

MVP

0.21

MPC

0.45

ClinPred

0.024

GERP RS

5.3

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.066

gMVP

0.31

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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