Genetic Variant RGPD2:p.Gly1429Glu (chr2-87782738-C-T) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001078170.3(RGPD2):c.4286G>A(p.Gly1429Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000021 ( 0 hom., cov: 8)

Exomes 𝑓: 0.00017 ( 11 hom. )

Failed GnomAD Quality Control

Consequence

RGPD2
NM_001078170.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.20

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 -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.01838702).

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.4286G>A	p.Gly1429Glu	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.4127G>A	p.Gly1376Glu	missense	Exon 20 of 23	NP_001380542.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RGPD2	ENST00000398146.5	TSL:1 MANE Select	c.4286G>A	p.Gly1429Glu	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
RGPD2	ENST00000971290.1		c.4283G>A	p.Gly1428Glu	missense	Exon 20 of 23	ENSP00000641349.1
RGPD2	ENST00000494592.1	TSL:1	n.-69G>A		upstream_gene	N/A

Frequencies

GnomAD3 genomes

AF:

0.0000208

AC:

AN:

47992

Hom.:

Cov.:

show subpopulations

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:

0.00172

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000381

AC:

AN:

44632

AF XY:

0.000580

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:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000172

AC:

207

AN:

1200910

Hom.:

Cov.:

AF XY:

0.000255

AC XY:

153

AN XY:

600740

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

29814

American (AMR)

AF:

0.0000265

AC:

AN:

37778

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22638

East Asian (EAS)

AF:

0.00

AC:

AN:

37632

South Asian (SAS)

AF:

0.00250

AC:

186

AN:

74298

European-Finnish (FIN)

AF:

0.00

AC:

AN:

43872

Middle Eastern (MID)

AF:

0.000287

AC:

AN:

3488

European-Non Finnish (NFE)

AF:

0.0000100

AC:

AN:

900272

Other (OTH)

AF:

0.000196

AC:

AN:

51118

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.486

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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: AS_VQSR

AF:

0.0000208

AC:

AN:

48120

Hom.:

Cov.:

AF XY:

0.0000446

AC XY:

AN XY:

22410

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

19184

American (AMR)

AF:

0.00

AC:

AN:

3622

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1004

East Asian (EAS)

AF:

0.00

AC:

AN:

1078

South Asian (SAS)

AF:

0.00171

AC:

AN:

584

European-Finnish (FIN)

AF:

0.00

AC:

AN:

2426

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

19274

Other (OTH)

AF:

0.00

AC:

AN:

516

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000936

Hom.:

ExAC

AF:

0.0000298

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

Uncertain

0.44

BayesDel_addAF

Benign

-0.43

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.12

Eigen

Benign

-0.15

Eigen_PC

Benign

-0.14

FATHMM_MKL

Uncertain

0.77

LIST_S2

Uncertain

0.89

M_CAP

Benign

0.010

MetaRNN

Benign

0.018

MetaSVM

Benign

-0.93

MutationAssessor

Benign

0.98

PhyloP100

3.2

PrimateAI

Uncertain

0.73

PROVEAN

Pathogenic

-4.6

REVEL

Benign

0.13

Sift

Benign

0.33

Sift4G

Benign

0.69

Vest4

0.39

MutPred

0.57

Gain of solvent accessibility (P = 0.024)

MVP

0.48

ClinPred

0.18

GERP RS

2.3

Varity_R

0.44

gMVP

0.012

Mutation Taster

=93/7

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over