Variant 2-112388083-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The ENST00000302558.8(RGPD8):c.4862C>T(p.Ser1621Phe) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00023 ( 0 hom., cov: 16)

Exomes 𝑓: 0.00022 ( 4 hom. )

Failed GnomAD Quality Control

Consequence

RGPD8
ENST00000302558.8 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.0620

Variant links:

Genes affected

RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) 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]

RGPD8 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.02273038).

BP6

Variant 2-112388083-G-A is Benign according to our data. Variant chr2-112388083-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 2362273.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD8	NM_001164463.1 linkuse as main transcript	c.4862C>T	p.Ser1621Phe	missense_variant	20/23	ENST00000302558.8	NP_001157935.1	O14715

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD8	ENST00000302558.8 linkuse as main transcript	c.4862C>T	p.Ser1621Phe	missense_variant	20/23	1	NM_001164463.1	ENSP00000306637.3		O14715
RGPD8	ENST00000409750.5 linkuse as main transcript	c.4442C>T	p.Ser1481Phe	missense_variant	19/22	1		ENSP00000386511.1		J3KQ37

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

120850

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.0000944

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000172

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000216

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000388

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000220

AC:

221

AN:

1005546

Hom.:

Cov.:

AF XY:

0.000228

AC XY:

115

AN XY:

504836

show subpopulations

Gnomad4 AFR exome

AF:

0.0000432

Gnomad4 AMR exome

AF:

0.000125

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000355

Gnomad4 SAS exome

AF:

0.0000329

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000254

Gnomad4 OTH exome

AF:

0.000224

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000232

AC:

AN:

120948

Hom.:

Cov.:

AF XY:

0.000139

AC XY:

AN XY:

57750

show subpopulations

Gnomad4 AFR

AF:

0.0000941

Gnomad4 AMR

AF:

0.000172

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000217

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000388

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000520

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Ambry Genetics

Oct 12, 2021

This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.073

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.77

CADD

Benign

5.5

DANN

Benign

0.17

DEOGEN2

Benign

0.0056

T;T

Eigen

Benign

-1.6

Eigen_PC

Benign

-1.6

FATHMM_MKL

Benign

0.0026

LIST_S2

Benign

0.13

T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.023

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.40

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

0.60

N;N

REVEL

Benign

0.012

Sift

Benign

0.33

T;T

Sift4G

Benign

0.54

T;T

Polyphen

0.0

B;.

Vest4

0.081

MutPred

0.28

Gain of helix (P = 0.0034);.;

MVP

0.040

ClinPred

0.029

GERP RS

0.66

Varity_R

0.056

gMVP

0.023

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