chr2-87783128-G-A

Variant names:

• chr2-87783128-G-A
• NM_001078170.3:c.3896C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001078170.3(RGPD2):​c.3896C>T​(p.Ala1299Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 9)
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24631393).

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.3896C>T	p.Ala1299Val	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.3737C>T	p.Ala1246Val	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.3896C>T	p.Ala1299Val	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000971290.1		c.3893C>T	p.Ala1298Val	missense	Exon 20 of 23	ENSP00000641349.1

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 9

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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T
Eigen	Benign	0.085
Eigen_PC	Benign	-0.0057
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.97	D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.25	T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		5.4
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	D
REVEL	Benign	0.099
Sift	Uncertain	0.018	D
Sift4G	Uncertain	0.015	D
Vest4		0.17
MutPred		0.22		Gain of methylation at K1300 (P = 0.0404)
MVP		0.095
ClinPred		0.90	D
GERP RS		1.4
Varity_R		0.19
gMVP		0.033
Mutation Taster		=97/3	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

hg19: chr2-88082647;