rs747249741

Variant names:

• chr2-87783163-A-C
• rs747249741
• NM_001078170.3:c.3861T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-87783163-A-C
• chr2-87783163-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001078170.3(RGPD2):​c.3861T>G​(p.Ser1287Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. S1287I) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.000043 (0 hom., cov: 9)
  • Exomes 𝑓: 0.000049 (2 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.16
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23993436).

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.3861T>G	p.Ser1287Arg	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.3702T>G	p.Ser1234Arg	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.3861T>G	p.Ser1287Arg	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000971290.1		c.3858T>G	p.Ser1286Arg	missense	Exon 20 of 23	ENSP00000641349.1

Frequencies

GnomAD3 genomes AF: 0.0000427 AC: 3 AN: 70242 Hom.: 0 Cov.: 9

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: 0.0000942

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000401 AC: 6 AN: 149646 AF XY: 0.0000250

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: 0.0000933

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000495 AC: 65 AN: 1313484 Hom.: 2 Cov.: 20 AF XY: 0.0000471 AC XY: 31 AN XY: 657794

African (AFR) AF: 0.0000315 AC: 1 AN: 31784

American (AMR) AF: 0.0000232 AC: 1 AN: 43186

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24992

East Asian (EAS) AF: 0.00 AC: 0 AN: 38456

South Asian (SAS) AF: 0.00 AC: 0 AN: 81818

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52240

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3800

European-Non Finnish (NFE) AF: 0.0000642 AC: 63 AN: 982022

Other (OTH) AF: 0.00 AC: 0 AN: 55186

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000427 AC: 3 AN: 70242 Hom.: 0 Cov.: 9 AF XY: 0.0000305 AC XY: 1 AN XY: 32782

African (AFR) AF: 0.00 AC: 0 AN: 24504

American (AMR) AF: 0.00 AC: 0 AN: 4948

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 1728

East Asian (EAS) AF: 0.00 AC: 0 AN: 1630

South Asian (SAS) AF: 0.00 AC: 0 AN: 994

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 3338

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 94

European-Non Finnish (NFE) AF: 0.0000942 AC: 3 AN: 31854

Other (OTH) AF: 0.00 AC: 0 AN: 698

Alfa AF: 0.000158 Hom.: 0

ExAC AF: 0.0000349 AC: 4

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	Pathogenic	0.69
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Uncertain	1.0
DEOGEN2	Benign	0.20	T
Eigen	Benign	0.080
Eigen_PC	Benign	-0.11
FATHMM_MKL	Benign	0.74	D
LIST_S2	Uncertain	0.89	D
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.2
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-3.5	D
REVEL	Benign	0.13
Sift	Uncertain	0.010	D
Sift4G	Uncertain	0.0050	D
Vest4		0.42
MutPred		0.36		Gain of methylation at S1287 (P = 0.016)
MVP		0.16
ClinPred		0.45	T
GERP RS		-0.31
Varity_R		0.32
gMVP		0.084
Mutation Taster		=88/12	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: rs747249741; hg19: chr2-88082682;