2-87782520-C-T

Variant names:

• chr2-87782520-C-T
• NM_001078170.3:c.4504G>A

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001078170.3(RGPD2):​c.4504G>A​(p.Gly1502Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 0)
  • Exomes 𝑓: 0.000012 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.388

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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0870963).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.4504G>A	p.Gly1502Ser	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.4504G>A	p.Gly1502Ser	missense_variant	Exon 20 of 23	1	NM_001078170.3	ENSP00000381214.3
RGPD2	ENST00000494592.1	n.150G>A		non_coding_transcript_exon_variant	Exon 1 of 2	1

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000121 AC: 4 AN: 331224 Hom.: 0 Cov.: 0 AF XY: 0.0000115 AC XY: 2 AN XY: 173626

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.0000546

Gnomad4 NFE exome AF: 0.0000153

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jun 29, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4504G>A (p.G1502S) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a G to A substitution at nucleotide position 4504, causing the glycine (G) at amino acid position 1502 to be replaced by a serine (S). 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	0.087
BayesDel_addAF	Benign	-0.28	T
BayesDel_noAF	Benign	-0.65
CADD	Benign	6.4
DANN	Benign	0.94
DEOGEN2	Benign	0.022	T;.
Eigen	Benign	-0.71
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.13	N
LIST_S2	Benign	0.77	T;T
M_CAP	Benign	0.0049	T
MetaRNN	Benign	0.087	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L;.
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	-1.9	N;.
REVEL	Benign	0.019
Sift	Benign	0.073	T;.
Sift4G	Benign	0.16	T;.
Vest4		0.051
MutPred		0.23		Gain of glycosylation at G1502 (P = 0.0131);Gain of glycosylation at G1502 (P = 0.0131);
MVP		0.040
ClinPred		0.20	T
GERP RS		2.3
Varity_R		0.054
gMVP		0.016

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: chr2-88082039;