chr2-87782525-A-G

Variant names:

• chr2-87782525-A-G
• rs759380272
• NM_001078170.3:c.4499T>C

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001078170.3(RGPD2):​c.4499T>C​(p.Ile1500Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0034 (4 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.772
• Publications: 2 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: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.005881548).

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.4499T>C	p.Ile1500Thr	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.4340T>C	p.Ile1447Thr	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.4499T>C	p.Ile1500Thr	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000494592.1	TSL:1	n.145T>C		non_coding_transcript_exon	Exon 1 of 2
	RGPD2	ENST00000971290.1		c.4496T>C	p.Ile1499Thr	missense	Exon 20 of 23	ENSP00000641349.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 176 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMR 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: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.00156 AC: 20 AN: 12792 AF XY: 0.00205

Gnomad AFR exome AF: 0.000403

Gnomad AMR exome AF: 0.00287

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00283

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00338 AC: 1159 AN: 342468 Hom.: 4 Cov.: 0 AF XY: 0.00336 AC XY: 603 AN XY: 179678

African (AFR) AF: 0.000797 AC: 9 AN: 11286

American (AMR) AF: 0.00297 AC: 44 AN: 14830

Ashkenazi Jewish (ASJ) AF: 0.00184 AC: 20 AN: 10882

East Asian (EAS) AF: 0.00 AC: 0 AN: 22570

South Asian (SAS) AF: 0.00167 AC: 66 AN: 39490

European-Finnish (FIN) AF: 0.000734 AC: 14 AN: 19078

Middle Eastern (MID) AF: 0.00207 AC: 3 AN: 1452

European-Non Finnish (NFE) AF: 0.00460 AC: 931 AN: 202604

Other (OTH) AF: 0.00355 AC: 72 AN: 20276

GnomAD4 genome Data not reliable, filtered out with message: AC0;AS_VQSR AF: 0.00 AC: 0 AN: 176 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 86

African (AFR) AF: 0.00 AC: 0 AN: 98

American (AMR) AF: 0.00 AC: 0 AN: 30

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.00 AC: 0 AN: 20

South Asian (SAS) AF: 0.00 AC: 0 AN: 6

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12

Other (OTH) AF: 0.00 AC: 0 AN: 4

Alfa AF: 0.000843 Hom.: 0

ExAC AF: 0.00229 AC: 2

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	0.10
BayesDel_addAF	Benign	-0.68	T
BayesDel_noAF	Benign	-0.76
CADD	Benign	0.39
DANN	Benign	0.67
DEOGEN2	Benign	0.0052	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.050	N
LIST_S2	Benign	0.52	T
M_CAP	Benign	0.0018	T
MetaRNN	Benign	0.0059	T
MetaSVM	Benign	-0.99	T
MutationAssessor	Benign	1.1	L
PhyloP100		-0.77
PrimateAI	Uncertain	0.54	T
PROVEAN	Benign	0.020	N
REVEL	Benign	0.0050
Sift	Benign	1.0	T
Sift4G	Benign	0.93	T
Vest4		0.043
MutPred		0.23		Loss of stability (P = 0.0126)
MVP		0.048
ClinPred		0.0022	T
GERP RS		-4.3
Varity_R		0.035
gMVP		0.0054
Mutation Taster		=97/3	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: rs759380272; hg19: chr2-88082044;