2-86977863-C-G

Variant names:

• chr2-86977863-C-G
• NM_001382344.1:c.2395C>G

Variant summary

Our verdict is Likely benign. The variant received -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
• Publications: 0 publications found

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

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.23993278).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001382344.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD1	NM_001382344.1	MANE Select	c.2395C>G	p.Pro799Ala	missense	Exon 17 of 23	NP_001369273.1	A0A286YES2
	RGPD1	NM_001410915.1		c.2395C>G	p.Pro799Ala	missense	Exon 17 of 23	NP_001397844.1	F8VYC4
	RGPD1	NM_001024457.4		c.2371C>G	p.Pro791Ala	missense	Exon 17 of 23	NP_001019628.3	P0DJD0

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD1	ENST00000641458.2	MANE Select	c.2395C>G	p.Pro799Ala	missense	Exon 17 of 23	ENSP00000492954.1	A0A286YES2
	RGPD1	ENST00000398193.8	TSL:1	c.2395C>G	p.Pro799Ala	missense	Exon 17 of 23	ENSP00000381253.3	F8VYC4
	RGPD1	ENST00000428128.1	TSL:1	n.*314C>G		non_coding_transcript_exon	Exon 4 of 10	ENSP00000402729.1	H7C1V8

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

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000244 AC: 3 AN: 12320

American (AMR) AF: 0.00 AC: 0 AN: 18482

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 10532

East Asian (EAS) AF: 0.00 AC: 0 AN: 32310

South Asian (SAS) AF: 0.00 AC: 0 AN: 46674

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 37060

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 1694

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 285866

Other (OTH) AF: 0.00 AC: 0 AN: 23506

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 5

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
Eigen	Benign	0.12
Eigen_PC	Benign	0.024
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0082	T
MetaRNN	Benign	0.24	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		6.4
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-3.9	D
REVEL	Benign	0.16
Sift	Benign	0.12	T
Sift4G	Benign	1.0	T
Polyphen		1.0	D
Vest4		0.40
MutPred		0.20		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
Mutation Taster		=95/5	polymorphism

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

Other links and lift over

hg19: chr2-87204986;