Variant 2-87782888-T-C details in Genebe, Genetics Data Aggregator

Variant summary

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

The ENST00000398146.5(RGPD2):c.4136A>G(p.Asn1379Ser) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 18)

Exomes 𝑓: 0.000049 ( 3 hom. )

Failed GnomAD Quality Control

Consequence

RGPD2
ENST00000398146.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.98

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:

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=0.30017853).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD2	NM_001078170.3 linkuse as main transcript	c.4136A>G	p.Asn1379Ser	missense_variant	20/23	ENST00000398146.5	NP_001071638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD2	ENST00000398146.5 linkuse as main transcript	c.4136A>G	p.Asn1379Ser	missense_variant	20/23	1	NM_001078170.3	ENSP00000381214	P1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

144196

Hom.:

Cov.:

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:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000306

Gnomad OTH

AF:

0.000516

GnomAD3 exomes

AF:

0.0000508

AC:

AN:

118138

Hom.:

AF XY:

0.0000660

AC XY:

AN XY:

60614

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000975

Gnomad OTH exome

AF:

0.000331

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000487

AC:

AN:

1457022

Hom.:

Cov.:

AF XY:

0.0000455

AC XY:

AN XY:

724920

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000224

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000613

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.0000208

AC:

AN:

144196

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

69848

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.0000306

Gnomad4 OTH

AF:

0.000516

Bravo

AF:

0.0000378

ExAC

AF:

0.0000526

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

Jun 07, 2023

The c.4136A>G (p.N1379S) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a A to G substitution at nucleotide position 4136, causing the asparagine (N) at amino acid position 1379 to be replaced by a serine (S). 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

0.24

BayesDel_addAF

Benign

-0.39

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.11

T;.

Eigen

Uncertain

0.19

Eigen_PC

Benign

0.087

FATHMM_MKL

Uncertain

0.87

LIST_S2

Uncertain

0.94

D;D

M_CAP

Benign

0.0064

MetaRNN

Benign

0.30

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.3

M;.

MutationTaster

Benign

0.99

N;N;N

PrimateAI

Pathogenic

0.85

PROVEAN

Uncertain

-3.4

D;.

REVEL

Benign

0.25

Sift

Uncertain

0.018

D;.

Sift4G

Benign

0.38

T;.

Vest4

0.34

MutPred

0.64

Loss of ubiquitination at K1383 (P = 0.1101);Loss of ubiquitination at K1383 (P = 0.1101);

MVP

0.067

ClinPred

0.28

GERP RS

2.3

Varity_R

0.18

gMVP

0.0096

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