2-87782945-T-A

Position:

• chr2-87782945-T-A

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2 PP3

The NM_001078170.3(RGPD2):​c.4079A>T​(p.Asp1360Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic 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: 7.84

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 3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.84

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.4079A>T	p.Asp1360Val	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.4079A>T	p.Asp1360Val	missense_variant	20/23	1	NM_001078170.3	ENSP00000381214.3

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD4 exome Cov.: 31

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

Jan 17, 2024

The c.4079A>T (p.D1360V) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a A to T substitution at nucleotide position 4079, causing the aspartic acid (D) at amino acid position 1360 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	Uncertain	0.52
BayesDel_addAF	Pathogenic	0.25	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Benign	0.97
DEOGEN2	Benign	0.18	T;.
Eigen	Benign	0.15
Eigen_PC	Benign	0.062
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.96	D;D
M_CAP	Benign	0.039	D
MetaRNN	Pathogenic	0.84	D;D
MetaSVM	Benign	-0.88	T
MutationAssessor	Uncertain	2.1	M;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-6.0	D;.
REVEL	Uncertain	0.42
Sift	Benign	0.064	T;.
Sift4G	Uncertain	0.0030	D;.
Vest4		0.86
MutPred		0.71		Gain of MoRF binding (P = 0.019);Gain of MoRF binding (P = 0.019);
MVP		0.40
ClinPred		0.97	D
GERP RS		2.4
Varity_R		0.38
gMVP		0.079

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: chr2-88082464;