2-86986834-A-G

Variant names:

• chr2-86986834-A-G
• rs1681479376
• NM_001382344.1:c.3935A>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.3935A>G​(p.Glu1312Gly) variant causes a missense change involving the alteration of a conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000012 (0 hom., cov: 12)
  • Exomes 𝑓: 0.0000014 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD1 NM_001382344.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 9.12
• 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=0.26051384).

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.3935A>G	p.Glu1312Gly	missense	Exon 20 of 23	NP_001369273.1	A0A286YES2
	RGPD1	NM_001410915.1		c.3935A>G	p.Glu1312Gly	missense	Exon 20 of 23	NP_001397844.1	F8VYC4
	RGPD1	NM_001024457.4		c.3911A>G	p.Glu1304Gly	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.3935A>G	p.Glu1312Gly	missense	Exon 20 of 23	ENSP00000492954.1	A0A286YES2
	RGPD1	ENST00000398193.8	TSL:1	c.3935A>G	p.Glu1312Gly	missense	Exon 20 of 23	ENSP00000381253.3	F8VYC4
	RGPD1	ENST00000428128.1	TSL:1	n.*1854A>G		non_coding_transcript_exon	Exon 7 of 10	ENSP00000402729.1	H7C1V8

Frequencies

GnomAD3 genomes AF: 0.0000115 AC: 1 AN: 86754 Hom.: 0 Cov.: 12

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000200

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000143 AC: 2 AN: 1403342 Hom.: 0 Cov.: 24 AF XY: 0.00 AC XY: 0 AN XY: 701698

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

African (AFR) AF: 0.00 AC: 0 AN: 24004

American (AMR) AF: 0.00 AC: 0 AN: 44442

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25828

East Asian (EAS) AF: 0.00 AC: 0 AN: 39226

South Asian (SAS) AF: 0.00 AC: 0 AN: 85372

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53152

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4010

European-Non Finnish (NFE) AF: 0.00000187 AC: 2 AN: 1069276

Other (OTH) AF: 0.00 AC: 0 AN: 58032

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.00233887), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000115 AC: 1 AN: 86754 Hom.: 0 Cov.: 12 AF XY: 0.00 AC XY: 0 AN XY: 40824

⚠️ 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: 13324

American (AMR) AF: 0.00 AC: 0 AN: 7910

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 2704

East Asian (EAS) AF: 0.00 AC: 0 AN: 2964

South Asian (SAS) AF: 0.00 AC: 0 AN: 2272

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 5550

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 142

European-Non Finnish (NFE) AF: 0.0000200 AC: 1 AN: 50106

Other (OTH) AF: 0.00 AC: 0 AN: 1054

⚠️ 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.

Alfa AF: 0.00 Hom.: 0

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	0.15
BayesDel_addAF	Benign	-0.13	T
BayesDel_noAF	Benign	-0.42
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.21	T
Eigen	Uncertain	0.29
Eigen_PC	Benign	0.22
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Uncertain	0.95	D
M_CAP	Benign	0.015	T
MetaRNN	Benign	0.26	T
MetaSVM	Benign	-0.97	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		9.1
PrimateAI	Uncertain	0.63	T
PROVEAN	Uncertain	-4.3	D
REVEL	Benign	0.23
Sift	Uncertain	0.0080	D
Sift4G	Benign	0.22	T
Polyphen		1.0	D
Vest4		0.20
MutPred		0.10		Loss of solvent accessibility (P = 0.0769)
MVP		0.29
ClinPred		0.92	D
GERP RS		2.4
Varity_R		0.18
gMVP		0.024
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: rs1681479376; hg19: chr2-87213957;