Variant 2-87772238-G-A details in Genebe, Genetics Data Aggregator

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

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]

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=0.2722708).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD2	NM_001078170.3 link	c.5167C>T	p.Leu1723Phe	missense_variant	22/23	ENST00000398146.5	NP_001071638.2	P0DJD1B4DYH0
RGPD2	NM_001393613.1 link	c.5008C>T	p.Leu1670Phe	missense_variant	22/23		NP_001380542.1
RGPD2	XM_017004845.2 link	c.5401C>T	p.Leu1801Phe	missense_variant	25/26		XP_016860334.2
RGPD2	XM_047445734.1 link	c.5326C>T	p.Leu1776Phe	missense_variant	24/25		XP_047301690.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD2	ENST00000398146.5 link	c.5167C>T	p.Leu1723Phe	missense_variant	22/23	1	NM_001078170.3	ENSP00000381214.3		P0DJD1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

125948

Hom.:

Cov.:

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:

AN:

1263376

Hom.:

Cov.:

AF XY:

0.0000394

AC XY:

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:

AN:

125948

Hom.:

Cov.:

AF XY:

0.0000664

AC XY:

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.:

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

Oct 29, 2021

The 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

BayesDel_noAF

Benign

-0.51

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0097

T;.

Eigen

Benign

-0.47

Eigen_PC

Benign

-0.68

FATHMM_MKL

Benign

0.20

LIST_S2

Pathogenic

0.97

D;D

M_CAP

Benign

0.0038

MetaRNN

Benign

0.27

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

2.0

M;.

PrimateAI

Uncertain

0.78

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

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.

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