Variant chr2-86913883-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The ENST00000398193.8(RGPD1):c.34C>G(p.Leu12Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00229 in 147,610 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/13 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0023 ( 4 hom., cov: 27)

Exomes 𝑓: 0.0015 ( 57 hom. )

Failed GnomAD Quality Control

Consequence

RGPD1
ENST00000398193.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.406

Variant links:

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) 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]

RGPD1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005818963).

BP6

Variant 2-86913883-C-G is Benign according to our data. Variant chr2-86913883-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 3250624.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001410915.1 linkuse as main transcript	c.34C>G	p.Leu12Val	missense_variant	1/23		NP_001397844.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD1	ENST00000398193.8 linkuse as main transcript	c.34C>G	p.Leu12Val	missense_variant	1/23	1		ENSP00000381253	P4
RGPD1	ENST00000641339.1 linkuse as main transcript	c.34C>G	p.Leu12Val	missense_variant, NMD_transcript_variant	1/5			ENSP00000492933

Frequencies

GnomAD3 genomes

AF:

0.00230

AC:

339

AN:

147518

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000820

Gnomad AMI

AF:

0.0403

Gnomad AMR

AF:

0.00216

Gnomad ASJ

AF:

0.00686

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00108

Gnomad FIN

AF:

0.000102

Gnomad MID

AF:

0.00980

Gnomad NFE

AF:

0.00310

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000680

AC:

157

AN:

230848

Hom.:

AF XY:

0.000663

AC XY:

AN XY:

125208

show subpopulations

Gnomad AFR exome

AF:

0.000449

Gnomad AMR exome

AF:

0.000424

Gnomad ASJ exome

AF:

0.00286

Gnomad EAS exome

AF:

0.0000577

Gnomad SAS exome

AF:

0.000215

Gnomad FIN exome

AF:

0.000100

Gnomad NFE exome

AF:

0.000855

Gnomad OTH exome

AF:

0.00210

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00146

AC:

2075

AN:

1423434

Hom.:

Cov.:

AF XY:

0.00144

AC XY:

1017

AN XY:

707230

show subpopulations

Gnomad4 AFR exome

AF:

0.000553

Gnomad4 AMR exome

AF:

0.000695

Gnomad4 ASJ exome

AF:

0.00634

Gnomad4 EAS exome

AF:

0.000108

Gnomad4 SAS exome

AF:

0.000370

Gnomad4 FIN exome

AF:

0.000784

Gnomad4 NFE exome

AF:

0.00150

Gnomad4 OTH exome

AF:

0.00247

GnomAD4 genome

AF:

0.00229

AC:

338

AN:

147610

Hom.:

Cov.:

AF XY:

0.00204

AC XY:

147

AN XY:

71950

show subpopulations

Gnomad4 AFR

AF:

0.000818

Gnomad4 AMR

AF:

0.00215

Gnomad4 ASJ

AF:

0.00686

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00109

Gnomad4 FIN

AF:

0.000102

Gnomad4 NFE

AF:

0.00309

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00439

Hom.:

ExAC

AF:

0.000482

AC:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

RGPD1: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.067

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.70

CADD

Benign

2.3

DANN

Benign

0.61

Eigen

Benign

-0.89

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.0071

LIST_S2

Benign

0.45

M_CAP

Benign

0.011

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.99

MutationTaster

Benign

1.0

N;N

PROVEAN

Benign

1.1

REVEL

Benign

0.040

Sift

Benign

1.0

Sift4G

Benign

1.0

Vest4

0.14

MVP

0.014

ClinPred

0.0052

Splicing

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