2-87782867-C-G

Variant names:

• chr2-87782867-C-G
• rs776595471
• NM_001078170.3:c.4157G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PP3_Strong

The NM_001078170.3(RGPD2):​c.4157G>C​(p.Arg1386Pro) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 17)
  • Exomes 𝑓: 0.0000027 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.02

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

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.977

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.4157G>C	p.Arg1386Pro	missense_variant	Exon 20 of 23	ENST00000398146.5	NP_001071638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD2	ENST00000398146.5	c.4157G>C	p.Arg1386Pro	missense_variant	Exon 20 of 23	1	NM_001078170.3	ENSP00000381214.3
RGPD2	ENST00000494592.1	n.-198G>C		upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 17

GnomAD3 exomes AF: 0.0000177 AC: 2 AN: 112888 Hom.: 0 AF XY: 0.0000169 AC XY: 1 AN XY: 59176

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.000131

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS 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: 0.00000274 AC: 4 AN: 1457244 Hom.: 0 Cov.: 30 AF XY: 0.00000276 AC XY: 2 AN XY: 725044

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000895

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 17

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.98
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Pathogenic	0.27
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.41	T;.
Eigen	Uncertain	0.53
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Pathogenic	0.99	D;D
M_CAP	Benign	0.041	D
MetaRNN	Pathogenic	0.98	D;D
MetaSVM	Uncertain	0.35	D
MutationAssessor	Pathogenic	3.9	H;.
PrimateAI	Pathogenic	0.79	T
PROVEAN	Pathogenic	-5.5	D;.
REVEL	Uncertain	0.56
Sift	Uncertain	0.0010	D;.
Sift4G	Uncertain	0.015	D;.
Vest4		0.90
MutPred		0.89		Loss of MoRF binding (P = 2e-04);Loss of MoRF binding (P = 2e-04);
MVP		0.40
ClinPred		1.0	D
GERP RS		2.3
Varity_R		0.85
gMVP		0.50

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

Other links and lift over

dbSNP: rs776595471; hg19: chr2-88082386;