2-87782669-A-T

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001078170.3(RGPD2):​c.4355T>A​(p.Ile1452Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 5)
Exomes 𝑓: 0.00015 ( 1 hom. )
Failed GnomAD Quality Control

Consequence

RGPD2
NM_001078170.3 missense

Scores

4
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.23
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 Likely_benign. Variant got -2 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.14524037).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RGPD2NM_001078170.3 linkuse as main transcriptc.4355T>A p.Ile1452Asn 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 linkuse as main transcriptc.4355T>A p.Ile1452Asn missense_variant 20/231 NM_001078170.3 ENSP00000381214.3 P0DJD1
RGPD2ENST00000494592.1 linkuse as main transcriptn.1T>A non_coding_transcript_exon_variant 1/21

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
2
AN:
20258
Hom.:
0
Cov.:
5
FAILED QC
Gnomad AFR
AF:
0.000107
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000687
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000378
AC:
2
AN:
52894
Hom.:
0
AF XY:
0.0000376
AC XY:
1
AN XY:
26578
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.000711
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000488
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000146
AC:
102
AN:
700802
Hom.:
1
Cov.:
9
AF XY:
0.000146
AC XY:
52
AN XY:
357072
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00195
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.000197
Gnomad4 NFE exome
AF:
0.000119
Gnomad4 OTH exome
AF:
0.000204
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000987
AC:
2
AN:
20258
Hom.:
0
Cov.:
5
AF XY:
0.000106
AC XY:
1
AN XY:
9422
show subpopulations
Gnomad4 AFR
AF:
0.000107
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000687
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000744
Hom.:
0
ExAC
AF:
0.0000674
AC:
3

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 GeneticsJun 06, 2023The c.4355T>A (p.I1452N) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a T to A substitution at nucleotide position 4355, causing the isoleucine (I) at amino acid position 1452 to be replaced by an asparagine (N). 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
Benign
0.32
BayesDel_addAF
Benign
-0.14
T
BayesDel_noAF
Benign
-0.44
CADD
Uncertain
23
DANN
Uncertain
0.98
DEOGEN2
Benign
0.078
T;.
Eigen
Benign
-0.11
Eigen_PC
Benign
-0.15
FATHMM_MKL
Benign
0.71
D
LIST_S2
Uncertain
0.88
D;D
M_CAP
Benign
0.014
T
MetaRNN
Benign
0.15
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.9
L;.
PrimateAI
Uncertain
0.69
T
PROVEAN
Uncertain
-3.4
D;.
REVEL
Benign
0.15
Sift
Benign
0.26
T;.
Sift4G
Benign
0.10
T;.
Vest4
0.68
MutPred
0.60
Gain of disorder (P = 0.0268);Gain of disorder (P = 0.0268);
MVP
0.36
ClinPred
0.33
T
GERP RS
2.3
Varity_R
0.34
gMVP
0.032

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: rs764274376; hg19: chr2-88082188; API