Variant 2-87782867-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001078170.3(RGPD2):c.4157G>A(p.Arg1386His) 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 0.000061 ( 0 hom., cov: 17)

Exomes 𝑓: 0.000038 ( 1 hom. )

Failed GnomAD Quality Control

Consequence

RGPD2
NM_001078170.3 missense

Scores

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]

RGPD2 links:

RGPD2 (HGNC:):

RGPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PP3

MetaRNN computational evidence supports a deleterious effect, 0.952

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD2	NM_001078170.3 linkuse as main transcript	c.4157G>A	p.Arg1386His	missense_variant	20/23	ENST00000398146.5	NP_001071638.2	P0DJD1B4DYH0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD2	ENST00000398146.5 linkuse as main transcript	c.4157G>A	p.Arg1386His	missense_variant	20/23	1	NM_001078170.3	ENSP00000381214.3		P0DJD1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

131712

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.000187

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:

0.0000165

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000797

AC:

AN:

112888

Hom.:

AF XY:

0.0000676

AC XY:

AN XY:

59176

show subpopulations

Gnomad AFR exome

AF:

0.000275

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.0000872

Gnomad SAS exome

AF:

0.000101

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000401

Gnomad OTH exome

AF:

0.000679

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000377

AC:

AN:

1457244

Hom.:

Cov.:

AF XY:

0.0000248

AC XY:

AN XY:

725044

show subpopulations

Gnomad4 AFR exome

AF:

0.000300

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000101

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.0000252

Gnomad4 OTH exome

AF:

0.000133

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000607

AC:

AN:

131712

Hom.:

Cov.:

AF XY:

0.0000634

AC XY:

AN XY:

63054

show subpopulations

Gnomad4 AFR

AF:

0.000187

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:

0.0000165

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.0000264

AC:

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

May 16, 2022

The c.4157G>A (p.R1386H) 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 4157, causing the arginine (R) at amino acid position 1386 to be replaced by a histidine (H). 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

Uncertain

0.53

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Uncertain

0.12

CADD

Uncertain

DANN

Uncertain

1.0

DEOGEN2

Benign

0.41

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.94

LIST_S2

Pathogenic

0.99

D;D

M_CAP

Benign

0.022

MetaRNN

Pathogenic

0.95

D;D

MetaSVM

Uncertain

0.23

MutationAssessor

Pathogenic

3.6

H;.

PrimateAI

Uncertain

0.78

PROVEAN

Uncertain

-3.9

D;.

REVEL

Uncertain

0.46

Sift

Uncertain

0.010

D;.

Sift4G

Uncertain

0.0070

D;.

Vest4

0.78

MutPred

0.89

Loss of MoRF binding (P = 0.0045);Loss of MoRF binding (P = 0.0045);

MVP

0.22

ClinPred

0.93

GERP RS

2.3

Varity_R

0.19

gMVP

0.15

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