chr17-18107173-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001388.5(DRG2):​c.1028G>T​(p.Ser343Ile) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)

Consequence

DRG2
NM_001388.5 missense

Scores

2
1
9

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 9.76
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.30624175).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DRG2NM_001388.5 linkuse as main transcriptc.1028G>T p.Ser343Ile missense_variant 13/13 ENST00000225729.8 NP_001379.1 P55039

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DRG2ENST00000225729.8 linkuse as main transcriptc.1028G>T p.Ser343Ile missense_variant 13/131 NM_001388.5 ENSP00000225729.3 P55039

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

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 submitterclinical testingAmbry GeneticsAug 21, 2024The c.1028G>T (p.S343I) alteration is located in exon 13 (coding exon 13) of the DRG2 gene. This alteration results from a G to T substitution at nucleotide position 1028, causing the serine (S) at amino acid position 343 to be replaced by an isoleucine (I). 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
0.71
BayesDel_addAF
Benign
-0.083
T
BayesDel_noAF
Benign
-0.14
CADD
Pathogenic
28
DANN
Uncertain
0.99
DEOGEN2
Benign
0.026
T
Eigen
Benign
0.038
Eigen_PC
Benign
0.15
FATHMM_MKL
Pathogenic
0.97
D
LIST_S2
Benign
0.41
T
M_CAP
Benign
0.083
D
MetaRNN
Benign
0.31
T
Vest4
0.37
MVP
0.48
ClinPred
0.95
D
GERP RS
4.7

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr17-18010487; API