2-87782915-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PP3_Moderate

The NM_001078170.3(RGPD2):​c.4109G>A​(p.Gly1370Asp) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000020 ( 0 hom., cov: 18)
Exomes 𝑓: 0.0000089 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RGPD2
NM_001078170.3 missense

Scores

8
5
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.02
Variant links:
Genes affected
RGPD2 (HGNC:32415): (RANBP2 like and GRIP domain containing 2) Predicted to contribute to GTPase activator activity. Predicted to be involved in NLS-bearing protein import into nucleus. Predicted to be part of nuclear pore. Predicted to be active in cytoplasm. [provided by Alliance of Genome Resources, Apr 2022]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PP3
MetaRNN computational evidence supports a deleterious effect, 0.939

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RGPD2NM_001078170.3 linkc.4109G>A p.Gly1370Asp missense_variant 20/23 ENST00000398146.5 NP_001071638.2 P0DJD1B4DYH0

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RGPD2ENST00000398146.5 linkc.4109G>A p.Gly1370Asp missense_variant 20/231 NM_001078170.3 ENSP00000381214.3 P0DJD1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
3
AN:
149204
Hom.:
0
Cov.:
18
FAILED QC
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000609
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
GnomAD3 exomes
AF:
0.0000605
AC:
15
AN:
248024
Hom.:
1
AF XY:
0.0000519
AC XY:
7
AN XY:
134828
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000818
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00000891
AC:
13
AN:
1458774
Hom.:
0
Cov.:
31
AF XY:
0.00000827
AC XY:
6
AN XY:
725694
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000227
Gnomad4 SAS exome
AF:
0.0000116
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
9.00e-7
Gnomad4 OTH exome
AF:
0.0000333
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000201
AC:
3
AN:
149204
Hom.:
0
Cov.:
18
AF XY:
0.00
AC XY:
0
AN XY:
72670
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000609
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0
ExAC
AF:
0.0000500
AC:
6

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 GeneticsFeb 28, 2023The c.4109G>A (p.G1370D) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a G to A substitution at nucleotide position 4109, causing the glycine (G) at amino acid position 1370 to be replaced by an aspartic acid (D). 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
0.86
BayesDel_addAF
Uncertain
0.11
D
BayesDel_noAF
Pathogenic
0.31
CADD
Pathogenic
26
DANN
Uncertain
0.98
DEOGEN2
Benign
0.41
T;.
Eigen
Benign
0.15
Eigen_PC
Benign
-0.056
FATHMM_MKL
Uncertain
0.93
D
LIST_S2
Pathogenic
1.0
D;D
M_CAP
Benign
0.029
D
MetaRNN
Pathogenic
0.94
D;D
MetaSVM
Uncertain
0.18
D
MutationAssessor
Pathogenic
4.0
H;.
PrimateAI
Pathogenic
0.87
D
PROVEAN
Pathogenic
-5.5
D;.
REVEL
Uncertain
0.53
Sift
Pathogenic
0.0
D;.
Sift4G
Benign
0.19
T;.
Vest4
0.93
MutPred
0.96
Loss of MoRF binding (P = 0.0344);Loss of MoRF binding (P = 0.0344);
MVP
0.40
ClinPred
0.63
D
GERP RS
1.4
Varity_R
0.69
gMVP
0.31

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.

Other links and lift over

dbSNP: rs779351695; hg19: chr2-88082434; API