Variant 17-18101933-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001388.5(DRG2):c.742A>C(p.Ile248Leu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00043 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

DRG2
NM_001388.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.27

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 Likely_benign. Variant got -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.26674366).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DRG2	NM_001388.5 linkuse as main transcript	c.742A>C	p.Ile248Leu	missense_variant	9/13	ENST00000225729.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DRG2	ENST00000225729.8 linkuse as main transcript	c.742A>C	p.Ile248Leu	missense_variant	9/13	1	NM_001388.5	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

151406

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000658

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000426

AC:

609

AN:

1430184

Hom.:

Cov.:

AF XY:

0.000381

AC XY:

271

AN XY:

712022

show subpopulations

Gnomad4 AFR exome

AF:

0.00105

Gnomad4 AMR exome

AF:

0.000229

Gnomad4 ASJ exome

AF:

0.000932

Gnomad4 EAS exome

AF:

0.00153

Gnomad4 SAS exome

AF:

0.0000234

Gnomad4 FIN exome

AF:

0.00134

Gnomad4 NFE exome

AF:

0.000334

Gnomad4 OTH exome

AF:

0.000810

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00000660

AC:

AN:

151524

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74106

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000657

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

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

Aug 30, 2022

The c.742A>C (p.I248L) alteration is located in exon 9 (coding exon 9) of the DRG2 gene. This alteration results from a A to C substitution at nucleotide position 742, causing the isoleucine (I) at amino acid position 248 to be replaced by a leucine (L). 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

0.64

BayesDel_addAF

Benign

-0.058

BayesDel_noAF

Benign

-0.32

CADD

Uncertain

DANN

Uncertain

0.99

DEOGEN2

Benign

0.044

T;T

Eigen

Uncertain

0.33

Eigen_PC

Uncertain

0.42

FATHMM_MKL

Uncertain

0.95

LIST_S2

Pathogenic

0.98

D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.95

MutationAssessor

Uncertain

2.8

M;.

MutationTaster

Benign

1.0

D;D;D

PrimateAI

Uncertain

0.77

PROVEAN

Benign

-1.8

N;N

REVEL

Benign

0.24

Sift

Uncertain

0.0010

D;D

Sift4G

Uncertain

0.0030

D;D

Polyphen

0.063

B;B

Vest4

0.53

MutPred

0.65

Gain of sheet (P = 0.0507);Gain of sheet (P = 0.0507);

MVP

0.17

MPC

0.63

ClinPred

0.89

GERP RS

5.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.52

gMVP

0.73

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