NM_001078170.3:c.3896C>T

Variant names:

• chr2-87783128-G-A
• NM_001078170.3:c.3896C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001078170.3(RGPD2):​c.3896C>T​(p.Ala1299Val) 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. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 9)
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.43

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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.24631393).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.3896C>T	p.Ala1299Val	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.3896C>T	p.Ala1299Val	missense_variant	Exon 20 of 23	1	NM_001078170.3	ENSP00000381214.3

Frequencies

GnomAD3 genomes Cov.: 9

GnomAD4 exome Cov.: 25

GnomAD4 genome Cov.: 9

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 16, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.3896C>T (p.A1299V) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a C to T substitution at nucleotide position 3896, causing the alanine (A) at amino acid position 1299 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	0.13
BayesDel_addAF	Benign	-0.22	T
BayesDel_noAF	Benign	-0.55
CADD	Benign	23
DANN	Uncertain	1.0
DEOGEN2	Benign	0.029	T;.
Eigen	Benign	0.085
Eigen_PC	Benign	-0.0057
FATHMM_MKL	Uncertain	0.85	D
LIST_S2	Pathogenic	0.97	D;D
M_CAP	Benign	0.0088	T
MetaRNN	Benign	0.25	T;T
MetaSVM	Benign	-0.95	T
MutationAssessor	Uncertain	2.2	M;.
PrimateAI	Uncertain	0.67	T
PROVEAN	Uncertain	-2.5	D;.
REVEL	Benign	0.099
Sift	Uncertain	0.018	D;.
Sift4G	Uncertain	0.015	D;.
Vest4		0.17
MutPred		0.22		Gain of methylation at K1300 (P = 0.0404);Gain of methylation at K1300 (P = 0.0404);
MVP		0.095
ClinPred		0.90	D
GERP RS		1.4
Varity_R		0.19
gMVP		0.033

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: chr2-88082647;