2-86986926-G-C

Variant names:

• chr2-86986926-G-C
• rs747372516
• NM_001382344.1:c.4027G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001382344.1(RGPD1):​c.4027G>C​(p.Glu1343Gln) variant causes a missense change involving the alteration of a conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000014 (0 hom., cov: 17)
  • Exomes 𝑓: 0.000057 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.78
• 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: Uncertain_significance. The variant received 0 ACMG points.

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.4027G>C	p.Glu1343Gln	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
	RGPD1	NM_001410915.1		c.4027G>C	p.Glu1343Gln	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
	RGPD1	NM_001024457.4		c.4003G>C	p.Glu1335Gln	missense	Exon 20 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.4027G>C	p.Glu1343Gln	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
	RGPD1	ENST00000398193.8	TSL:1	c.4027G>C	p.Glu1343Gln	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
	RGPD1	ENST00000428128.1	TSL:1	n.*1946G>C		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes AF: 0.0000143 AC: 2 AN: 139912 Hom.: 0 Cov.: 17

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.000154 AC: 25 AN: 162614 AF XY: 0.000170

Gnomad AFR exome AF: 0.000121

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000638

Gnomad NFE exome AF: 0.000287

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000571 AC: 83 AN: 1454548 Hom.: 0 Cov.: 31 AF XY: 0.0000746 AC XY: 54 AN XY: 723944

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

African (AFR) AF: 0.0000346 AC: 1 AN: 28872

American (AMR) AF: 0.00 AC: 0 AN: 44650

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26118

East Asian (EAS) AF: 0.00 AC: 0 AN: 39574

South Asian (SAS) AF: 0.00 AC: 0 AN: 86158

European-Finnish (FIN) AF: 0.0000562 AC: 3 AN: 53414

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4126

European-Non Finnish (NFE) AF: 0.0000684 AC: 76 AN: 1111632

Other (OTH) AF: 0.0000333 AC: 2 AN: 60004

⚠️ 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 Data not reliable, filtered out with message: AS_VQSR AF: 0.0000143 AC: 2 AN: 139912 Hom.: 0 Cov.: 17 AF XY: 0.0000146 AC XY: 1 AN XY: 68302

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

African (AFR) AF: 0.00 AC: 0 AN: 30630

American (AMR) AF: 0.00 AC: 0 AN: 14646

Ashkenazi Jewish (ASJ) AF: 0.000289 AC: 1 AN: 3466

East Asian (EAS) AF: 0.00 AC: 0 AN: 5018

South Asian (SAS) AF: 0.00 AC: 0 AN: 4738

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10516

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000148 AC: 1 AN: 67688

Other (OTH) AF: 0.00 AC: 0 AN: 1984

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

ExAC AF: 0.000217 AC: 25

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	Pathogenic	0.58
BayesDel_addAF	Benign	-0.098	T
BayesDel_noAF	Uncertain	-0.070
CADD	Uncertain	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.25	T
Eigen	Pathogenic	0.71
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.037	D
MetaRNN	Uncertain	0.47	T
MetaSVM	Uncertain	0.22	D
MutationAssessor	Pathogenic	4.0	H
PhyloP100		9.8
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.46
Sift	Pathogenic	0.0	D
Sift4G	Benign	0.095	T
Polyphen		1.0	D
Vest4		0.59
MVP		0.32
ClinPred		0.59	D
GERP RS		2.4
Varity_R		0.50
gMVP		0.042
Mutation Taster		=98/2	polymorphism

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

Other links and lift over

dbSNP: rs747372516; hg19: chr2-87214049;