2-87782790-T-C

Variant names:

• chr2-87782790-T-C
• rs1685459725
• NM_001078170.3:c.4234A>G

Variant summary

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

The NM_001078170.3(RGPD2):​c.4234A>G​(p.Met1412Val) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 8)
  • Exomes 𝑓: 0.0000021 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.00

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=0.36492288).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RGPD2	NM_001078170.3	c.4234A>G	p.Met1412Val	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.4234A>G	p.Met1412Val	missense_variant	Exon 20 of 23	1	NM_001078170.3	ENSP00000381214.3
RGPD2	ENST00000494592.1	n.-121A>G		upstream_gene_variant		1

Frequencies

GnomAD3 genomes Cov.: 8

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000212 AC: 3 AN: 1412234 Hom.: 0 Cov.: 26 AF XY: 0.00000142 AC XY: 1 AN XY: 703602

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000512

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 8

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Jul 22, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.4234A>G (p.M1412V) alteration is located in exon 20 (coding exon 20) of the RGPD2 gene. This alteration results from a A to G substitution at nucleotide position 4234, causing the methionine (M) at amino acid position 1412 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	0.19
BayesDel_addAF	Benign	-0.072	T
BayesDel_noAF	Benign	-0.34
CADD	Benign	21
DANN	Benign	0.81
DEOGEN2	Benign	0.084	T;.
Eigen	Uncertain	0.23
Eigen_PC	Benign	0.096
FATHMM_MKL	Uncertain	0.86	D
LIST_S2	Uncertain	0.86	D;D
M_CAP	Benign	0.0048	T
MetaRNN	Benign	0.36	T;T
MetaSVM	Benign	-0.91	T
MutationAssessor	Uncertain	2.5	M;.
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-2.6	D;.
REVEL	Benign	0.25
Sift	Benign	0.23	T;.
Sift4G	Benign	0.25	T;.
Vest4		0.48
MutPred		0.54		Gain of methylation at K1413 (P = 0.0383);Gain of methylation at K1413 (P = 0.0383);
MVP		0.088
ClinPred		0.43	T
GERP RS		2.3
Varity_R		0.16
gMVP		0.019

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

LitVar

Other links and lift over

dbSNP: rs1685459725; hg19: chr2-88082309;