2-87783036-C-A

Position:

• chr2-87783036-C-A

Variant summary

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

The NM_001078170.3(RGPD2):​c.3988G>T​(p.Val1330Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: 4.88

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]

RGPD2 (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/exons	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.3988G>T	p.Val1330Phe	missense_variant	20/23	ENST00000398146.5	NP_001071638.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD2	ENST00000398146.5	c.3988G>T	p.Val1330Phe	missense_variant	20/23	1	NM_001078170.3	ENSP00000381214.3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 18

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 17, 2022

The c.3988G>T (p.V1330F) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a G to T substitution at nucleotide position 3988, causing the valine (V) at amino acid position 1330 to be replaced by a phenylalanine (F). 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	Pathogenic	0.73
BayesDel_addAF	Uncertain	0.079	D
BayesDel_noAF	Benign	-0.12
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.43	T;.
Eigen	Uncertain	0.49
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.90	D
LIST_S2	Pathogenic	0.98	D;D
M_CAP	Benign	0.025	T
MetaRNN	Uncertain	0.46	T;T
MetaSVM	Benign	-0.31	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Uncertain	0.76	T
PROVEAN	Uncertain	-3.7	D;.
REVEL	Benign	0.27
Sift	Uncertain	0.0020	D;.
Sift4G	Benign	0.067	T;.
Vest4		0.72
MutPred		0.32		Loss of disorder (P = 0.1988);Loss of disorder (P = 0.1988);
MVP		0.28
ClinPred		0.99	D
GERP RS		2.4
Varity_R		0.68
gMVP		0.066

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: chr2-88082555;