chr2-87782907-C-G

Variant names:

• chr2-87782907-C-G
• rs754428835
• NM_001078170.3:c.4117G>C

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 1P and 0B. PP3

The NM_001078170.3(RGPD2):​c.4117G>C​(p.Asp1373His) variant causes a missense change. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 18)
  • Exomes 𝑓: 0.000015 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.94
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

• PP3: MetaRNN computational evidence supports a deleterious effect, 0.766

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001078170.3. 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
	RGPD2	NM_001078170.3	MANE Select	c.4117G>C	p.Asp1373His	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.3958G>C	p.Asp1320His	missense	Exon 20 of 23	NP_001380542.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD2	ENST00000398146.5	TSL:1 MANE Select	c.4117G>C	p.Asp1373His	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000971290.1		c.4114G>C	p.Asp1372His	missense	Exon 20 of 23	ENSP00000641349.1
	RGPD2	ENST00000494592.1	TSL:1	n.-238G>C		upstream_gene	N/A

Frequencies

GnomAD3 genomes Cov.: 18

GnomAD2 exomes AF: 0.0000363 AC: 9 AN: 247666 AF XY: 0.0000297

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000491

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000151 AC: 22 AN: 1458740 Hom.: 0 Cov.: 31 AF XY: 0.00000965 AC XY: 7 AN XY: 725672

⚠️ 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: 33384

American (AMR) AF: 0.00 AC: 0 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26106

East Asian (EAS) AF: 0.000505 AC: 20 AN: 39608

South Asian (SAS) AF: 0.00 AC: 0 AN: 86040

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53400

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

European-Non Finnish (NFE) AF: 0.00000180 AC: 2 AN: 1111232

Other (OTH) AF: 0.00 AC: 0 AN: 60134

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0.000000000000000111022), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Cov.: 18

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000334 AC: 4

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	Uncertain	0.49
BayesDel_addAF	Benign	-0.10	T
BayesDel_noAF	Uncertain	-0.050
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.30	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.23
FATHMM_MKL	Uncertain	0.93	D
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.014	T
MetaRNN	Pathogenic	0.77	D
MetaSVM	Uncertain	-0.19	T
MutationAssessor	Pathogenic	3.6	H
PhyloP100		3.9
PrimateAI	Pathogenic	0.88	D
PROVEAN	Pathogenic	-5.1	D
REVEL	Uncertain	0.44
Sift	Uncertain	0.0050	D
Sift4G	Benign	0.072	T
Vest4		0.69
MutPred		0.69		Gain of MoRF binding (P = 0.0427)
MVP		0.32
ClinPred		0.61	D
GERP RS		2.4
Varity_R		0.36
gMVP		0.042
Mutation Taster		=89/11	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: rs754428835; hg19: chr2-88082426;