Genetic Variant RGPD2:p.Lys1296Glu (chr2-87783138-T-C) – ACMG Classification: Likely_benign (-1 pts)

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_001078170.3(RGPD2):c.3886A>G(p.Lys1296Glu) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 9)

Exomes 𝑓: 7.2e-7 ( 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: 7.84

Publications

0 publications found

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 was made for transcript

Our verdict: Likely_benign. The variant received -1 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.30655193).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001078170.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD2	NM_001078170.3	MANE Select	c.3886A>G	p.Lys1296Glu	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.3727A>G	p.Lys1243Glu	missense	Exon 20 of 23	NP_001380542.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD2	ENST00000398146.5	TSL:1 MANE Select	c.3886A>G	p.Lys1296Glu	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000971290.1		c.3883A>G	p.Lys1295Glu	missense	Exon 20 of 23	ENSP00000641349.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

72548

Hom.:

Cov.:

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000606

AC:

AN:

164970

AF XY:

0.0000113

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000227

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

7.23e-7

AC:

AN:

1383714

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

691166

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32582

American (AMR)

AF:

0.0000226

AC:

AN:

44340

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25560

East Asian (EAS)

AF:

0.00

AC:

AN:

38902

South Asian (SAS)

AF:

0.00

AC:

AN:

84038

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52936

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3950

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1043828

Other (OTH)

AF:

0.00

AC:

AN:

57578

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

72548

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

33854

African (AFR)

AF:

0.00

AC:

AN:

24936

American (AMR)

AF:

0.00

AC:

AN:

5024

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1796

East Asian (EAS)

AF:

0.00

AC:

AN:

1682

South Asian (SAS)

AF:

0.00

AC:

AN:

996

European-Finnish (FIN)

AF:

0.00

AC:

AN:

3186

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

33666

Other (OTH)

AF:

0.00

AC:

AN:

726

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.00000863

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.081

BayesDel_noAF

Benign

-0.35

CADD

Uncertain

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.084

Eigen

Uncertain

0.39

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Uncertain

0.95

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.019

MetaRNN

Benign

0.31

MetaSVM

Benign

-0.61

MutationAssessor

Uncertain

2.4

PhyloP100

7.8

PrimateAI

Pathogenic

0.84

PROVEAN

Uncertain

-2.5

REVEL

Benign

0.13

Sift

Benign

0.22

Sift4G

Benign

0.20

Vest4

0.37

MutPred

0.25

Loss of ubiquitination at K1296 (P = 0.0381)

MVP

0.11

ClinPred

0.75

GERP RS

2.4

Varity_R

0.23

gMVP

0.026

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over