rs1685467707

Variant names:

• chr2-87782913-T-C
• rs1685467707
• NM_001078170.3:c.4111A>G

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001078170.3(RGPD2):​c.4111A>G​(p.Ile1371Val) 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. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 18)
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.02

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.37463522).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.4111A>G	p.Ile1371Val	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.4111A>G	p.Ile1371Val	missense_variant	Exon 20 of 23	1	NM_001078170.3	ENSP00000381214.3
RGPD2	ENST00000494592.1	n.-244A>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 18

Bravo AF: 0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Apr 09, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4111A>G (p.I1371V) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a A to G substitution at nucleotide position 4111, causing the isoleucine (I) at amino acid position 1371 to be replaced by a valine (V). 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	Benign	0.14
BayesDel_addAF	Benign	-0.18	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	20
DANN	Benign	0.89
DEOGEN2	Benign	0.010	T;.
Eigen	Benign	-0.15
Eigen_PC	Benign	-0.17
FATHMM_MKL	Uncertain	0.81	D
LIST_S2	Benign	0.75	T;T
M_CAP	Benign	0.0042	T
MetaRNN	Benign	0.37	T;T
MetaSVM	Benign	-0.93	T
MutationAssessor	Benign	1.0	L;.
PrimateAI	Uncertain	0.72	T
PROVEAN	Benign	-0.69	N;.
REVEL	Benign	0.14
Sift	Benign	0.57	T;.
Sift4G	Benign	0.35	T;.
Vest4		0.32
MutPred		0.48		Gain of MoRF binding (P = 0.0868);Gain of MoRF binding (P = 0.0868);
MVP		0.048
ClinPred		0.27	T
GERP RS		2.4
Varity_R		0.055
gMVP		0.0066

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: rs1685467707; hg19: chr2-88082432;