2-87772192-C-T

Variant names:

• chr2-87772192-C-T
• rs1323505860
• NM_001078170.3:c.5213G>A

Variant summary

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

The NM_001078170.3(RGPD2):​c.5213G>A​(p.Gly1738Glu) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000055 (0 hom., cov: 18)
  • Exomes 𝑓: 0.000024 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.65
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.04837936).

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.5213G>A	p.Gly1738Glu	missense	Exon 22 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.5054G>A	p.Gly1685Glu	missense	Exon 22 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.5213G>A	p.Gly1738Glu	missense	Exon 22 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000971290.1		c.5210G>A	p.Gly1737Glu	missense	Exon 22 of 23	ENSP00000641349.1

Frequencies

GnomAD3 genomes AF: 0.0000546 AC: 7 AN: 128140 Hom.: 0 Cov.: 18

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00167

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: 0.000202 AC: 2 AN: 9888 AF XY: 0.000181

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00136

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: 0.0000236 AC: 26 AN: 1103364 Hom.: 0 Cov.: 15 AF XY: 0.0000196 AC XY: 11 AN XY: 562606

African (AFR) AF: 0.00 AC: 0 AN: 23150

American (AMR) AF: 0.00 AC: 0 AN: 42648

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22690

East Asian (EAS) AF: 0.000612 AC: 23 AN: 37564

South Asian (SAS) AF: 0.00 AC: 0 AN: 73322

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52160

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3382

European-Non Finnish (NFE) AF: 0.00000125 AC: 1 AN: 800628

Other (OTH) AF: 0.0000418 AC: 2 AN: 47820

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000546 AC: 7 AN: 128236 Hom.: 0 Cov.: 18 AF XY: 0.0000325 AC XY: 2 AN XY: 61584

African (AFR) AF: 0.00 AC: 0 AN: 30832

American (AMR) AF: 0.00 AC: 0 AN: 12952

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3098

East Asian (EAS) AF: 0.00167 AC: 7 AN: 4192

South Asian (SAS) AF: 0.00 AC: 0 AN: 3282

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 9050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 278

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 61988

Other (OTH) AF: 0.00 AC: 0 AN: 1688

Alfa AF: 0.00 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.070
BayesDel_addAF	Benign	-0.50	T
BayesDel_noAF	Benign	-0.53
CADD	Benign	20
DANN	Benign	0.96
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-0.60
Eigen_PC	Benign	-0.69
FATHMM_MKL	Benign	0.41	N
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.0029	T
MetaRNN	Benign	0.048	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.85	N
PhyloP100		3.6
PrimateAI	Uncertain	0.74	T
PROVEAN	Benign	0.74	N
REVEL	Benign	0.13
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.0050	D
Vest4		0.23
MutPred		0.29		Loss of catalytic residue at P1734 (P = 0.0814)
MVP		0.17
ClinPred		0.19	T
Varity_R		0.31
gMVP		0.017
Mutation Taster		=94/6	polymorphism

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

Other links and lift over

dbSNP: rs1323505860; hg19: chr2-88071711;