2-87772232-C-T

Variant names:

• chr2-87772232-C-T
• NM_001078170.3:c.5173G>A

Variant summary

Our verdict is Likely benign. Variant got -1 ACMG points: 0P and 1B. BP4

The NM_001078170.3(RGPD2):​c.5173G>A​(p.Val1725Ile) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 16)
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.25

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 Likely_benign. Variant got -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.386217).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.5173G>A	p.Val1725Ile	missense_variant	Exon 22 of 23	ENST00000398146.5	NP_001071638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RGPD2	ENST00000398146.5	c.5173G>A	p.Val1725Ile	missense_variant	Exon 22 of 23	1	NM_001078170.3	ENSP00000381214.3

Frequencies

GnomAD3 genomes Cov.: 16

GnomAD4 exome Cov.: 18

GnomAD4 genome Cov.: 16

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

May 13, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.5173G>A (p.V1725I) alteration is located in exon 22 (coding exon 22) of the RGPD2 gene. This alteration results from a G to A substitution at nucleotide position 5173, causing the valine (V) at amino acid position 1725 to be replaced by an isoleucine (I). 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	0.10
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Benign	20
DANN	Benign	0.92
DEOGEN2	Benign	0.0078	T;.
Eigen	Benign	-0.091
Eigen_PC	Benign	-0.38
FATHMM_MKL	Benign	0.51	D
LIST_S2	Uncertain	0.97	D;D
M_CAP	Benign	0.0041	T
MetaRNN	Benign	0.39	T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Pathogenic	0.83	D
PROVEAN	Benign	-0.33	N;.
REVEL	Benign	0.17
Sift	Pathogenic	0.0	D;.
Sift4G	Pathogenic	0.0	D;.
Vest4		0.18
MutPred		0.64		Loss of catalytic residue at V1725 (P = 0.0155);Loss of catalytic residue at V1725 (P = 0.0155);
MVP		0.067
ClinPred		0.58	D
Varity_R		0.21
gMVP		0.035

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.040		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: chr2-88071751;