2-86977863-C-G

Position:

• chr2-86977863-C-G

Variant summary

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

The NM_001382344.1(RGPD1):​c.2395C>G​(p.Pro799Ala) 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: 5)
  • Exomes 𝑓: 0.0000064 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.40

Genes affected

RGPD1 (HGNC:32414): (RANBP2 like and GRIP domain containing 1) 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=0.23993278).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RGPD1	NM_001382344.1	c.2395C>G	p.Pro799Ala	missense_variant	17/23	ENST00000641458.2	NP_001369273.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RGPD1	ENST00000641458.2	c.2395C>G	p.Pro799Ala	missense_variant	17/23		NM_001382344.1	ENSP00000492954.1
RGPD1	ENST00000398193.8	c.2395C>G	p.Pro799Ala	missense_variant	17/23	1		ENSP00000381253.3
RGPD1	ENST00000428128.1	n.*314C>G		non_coding_transcript_exon_variant	4/10	1		ENSP00000402729.1
RGPD1	ENST00000428128.1	n.*314C>G		3_prime_UTR_variant	4/10	1		ENSP00000402729.1

Frequencies

GnomAD3 genomes Cov.: 5

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000640 AC: 3 AN: 468444 Hom.: 0 Cov.: 7 AF XY: 0.00000403 AC XY: 1 AN XY: 247948

Gnomad4 AFR exome AF: 0.000244

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: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 5

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

Sep 27, 2022

The c.2371C>G (p.P791A) alteration is located in exon 17 (coding exon 17) of the RGPD1 gene. This alteration results from a C to G substitution at nucleotide position 2371, causing the proline (P) at amino acid position 791 to be replaced by an alanine (A). 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	0.084
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.43
CADD	Uncertain	25
DANN	Benign	0.67
DEOGEN2	Benign	0.20	T;.;T;.
Eigen	Benign	0.12
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D;D;.;D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.24	T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M;.;M;.
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D;D;D;.
REVEL	Benign	0.16
Sift	Benign	0.12	T;T;T;.
Sift4G	Benign	1.0	T;T;T;.
Polyphen		1.0	.;D;.;.
Vest4		0.40
MutPred		0.20		.;Loss of catalytic residue at P799 (P = 0.0101);.;Loss of catalytic residue at P799 (P = 0.0101);
MVP		0.13
ClinPred		0.51	D
GERP RS		2.3
Varity_R		0.15
gMVP		0.042

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.13		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: chr2-87204986;