2-87772238-G-A

Variant summary

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

The NM_001078170.3(RGPD2):​c.5167C>T​(p.Leu1723Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000040 ( 0 hom., cov: 16)
Exomes 𝑓: 0.000050 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

RGPD2
NM_001078170.3 missense

Scores

2
2
15

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.37
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 -1 ACMG points.

BP4
Computational evidence support a benign effect (MetaRNN=0.2722708).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
RGPD2NM_001078170.3 linkc.5167C>T p.Leu1723Phe missense_variant 22/23 ENST00000398146.5 NP_001071638.2 P0DJD1B4DYH0
RGPD2NM_001393613.1 linkc.5008C>T p.Leu1670Phe missense_variant 22/23 NP_001380542.1
RGPD2XM_017004845.2 linkc.5401C>T p.Leu1801Phe missense_variant 25/26 XP_016860334.2
RGPD2XM_047445734.1 linkc.5326C>T p.Leu1776Phe missense_variant 24/25 XP_047301690.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
RGPD2ENST00000398146.5 linkc.5167C>T p.Leu1723Phe missense_variant 22/231 NM_001078170.3 ENSP00000381214.3 P0DJD1

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
5
AN:
125948
Hom.:
0
Cov.:
16
FAILED QC
Gnomad AFR
AF:
0.0000331
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:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000653
Gnomad OTH
AF:
0.00
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000499
AC:
63
AN:
1263376
Hom.:
0
Cov.:
19
AF XY:
0.0000394
AC XY:
25
AN XY:
634244
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000644
Gnomad4 OTH exome
AF:
0.0000377
GnomAD4 genome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.0000397
AC:
5
AN:
125948
Hom.:
0
Cov.:
16
AF XY:
0.0000664
AC XY:
4
AN XY:
60272
show subpopulations
Gnomad4 AFR
AF:
0.0000331
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000653
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0000843
Hom.:
0

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 GeneticsOct 29, 2021The c.5167C>T (p.L1723F) alteration is located in exon 22 (coding exon 22) of the RGPD2 gene. This alteration results from a C to T substitution at nucleotide position 5167, causing the leucine (L) at amino acid position 1723 to be replaced by a phenylalanine (F). 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
0.18
BayesDel_addAF
Benign
-0.19
T
BayesDel_noAF
Benign
-0.51
CADD
Benign
19
DANN
Uncertain
0.99
DEOGEN2
Benign
0.0097
T;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.68
FATHMM_MKL
Benign
0.20
N
LIST_S2
Pathogenic
0.97
D;D
M_CAP
Benign
0.0038
T
MetaRNN
Benign
0.27
T;T
MetaSVM
Benign
-0.96
T
MutationAssessor
Benign
2.0
M;.
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-0.57
N;.
REVEL
Benign
0.16
Sift
Pathogenic
0.0
D;.
Sift4G
Benign
0.072
T;.
Vest4
0.23
MVP
0.081
ClinPred
0.44
T
Varity_R
0.22
gMVP
0.036

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
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: rs1194466683; hg19: chr2-88071757; COSMIC: COSV59530247; COSMIC: COSV59530247; API