2-107854566-C-G

Variant names:

• chr2-107854566-C-G
• NM_182588.3:c.989C>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_182588.3(RGPD4):​c.989C>G​(p.Pro330Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 25)
• Consequence: RGPD4 NM_182588.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.96

Genes affected

RGPD4 (HGNC:32417): (RANBP2 like and GRIP domain containing 4) 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]

LOC124906057 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD4	NM_182588.3	c.989C>G	p.Pro330Arg	missense_variant	Exon 8 of 23	ENST00000408999.4	NP_872394.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD4	ENST00000408999.4	c.989C>G	p.Pro330Arg	missense_variant	Exon 8 of 23	1	NM_182588.3	ENSP00000386810.4

Frequencies

GnomAD3 genomes Cov.: 25

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 25

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jan 29, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.989C>G (p.P330R) alteration is located in exon 8 (coding exon 8) of the RGPD4 gene. This alteration results from a C to G substitution at nucleotide position 989, causing the proline (P) at amino acid position 330 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.54
BayesDel_addAF	Benign	-0.052	T
BayesDel_noAF	Benign	-0.31
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.18	T
Eigen	Uncertain	0.39
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.018	T
MetaRNN	Uncertain	0.73	D
MetaSVM	Benign	-0.68	T
MutationAssessor	Uncertain	2.5	M
PrimateAI	Pathogenic	0.84	D
PROVEAN	Pathogenic	-5.8	D
REVEL	Benign	0.24
Sift	Uncertain	0.0040	D
Sift4G	Uncertain	0.0090	D
Polyphen		1.0	D
Vest4		0.70
MutPred		0.48		Gain of MoRF binding (P = 0.0014);
MVP		0.19
ClinPred		0.97	D
GERP RS		2.9
Varity_R		0.50
gMVP		0.038

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-108471022;