chr2-87782703-T-C

Variant names:

• chr2-87782703-T-C
• rs751844623
• NM_001078170.3:c.4321A>G

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001078170.3(RGPD2):​c.4321A>G​(p.Lys1441Glu) 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 Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.00034 (0 hom., cov: 6)
  • Exomes 𝑓: 0.00035 (15 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 7.84
• 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.013915598).
• BP6: Variant 2-87782703-T-C is Benign according to our data. Variant chr2-87782703-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 3153642.Status of the report is criteria_provided_single_submitter, 1 stars.

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.4321A>G	p.Lys1441Glu	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.4162A>G	p.Lys1388Glu	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.4321A>G	p.Lys1441Glu	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000971290.1		c.4318A>G	p.Lys1440Glu	missense	Exon 20 of 23	ENSP00000641349.1
	RGPD2	ENST00000494592.1	TSL:1	n.-34A>G		upstream_gene	N/A

Frequencies

GnomAD3 genomes AF: 0.000374 AC: 13 AN: 34720 Hom.: 0 Cov.: 6

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000367

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0153

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: 0.00170 AC: 85 AN: 49854 AF XY: 0.00200

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0122

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00117

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000352 AC: 342 AN: 971164 Hom.: 15 Cov.: 13 AF XY: 0.000408 AC XY: 199 AN XY: 487970

African (AFR) AF: 0.0000758 AC: 2 AN: 26368

American (AMR) AF: 0.0000755 AC: 2 AN: 26496

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18540

East Asian (EAS) AF: 0.00848 AC: 300 AN: 35374

South Asian (SAS) AF: 0.000342 AC: 21 AN: 61444

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 34788

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2984

European-Non Finnish (NFE) AF: 0.00000277 AC: 2 AN: 721622

Other (OTH) AF: 0.000344 AC: 15 AN: 43548

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000344 AC: 12 AN: 34842 Hom.: 0 Cov.: 6 AF XY: 0.000492 AC XY: 8 AN XY: 16252

African (AFR) AF: 0.00 AC: 0 AN: 14880

American (AMR) AF: 0.000364 AC: 1 AN: 2744

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 650

East Asian (EAS) AF: 0.0141 AC: 11 AN: 780

South Asian (SAS) AF: 0.00 AC: 0 AN: 472

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 2062

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 96

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 12556

Other (OTH) AF: 0.00 AC: 0 AN: 396

Alfa AF: 0.00 Hom.: 0

ExAC AF: 0.000204 AC: 12

ClinVar

ClinVar submissions

Significance: Likely benign

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	0.29
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Uncertain	0.0
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T
Eigen	Uncertain	0.47
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.84	T
MetaRNN	Benign	0.014	T
MetaSVM	Benign	-0.49	T
MutationAssessor	Pathogenic	3.5	H
PhyloP100		7.8
PrimateAI	Pathogenic	0.79	T
PROVEAN	Uncertain	-3.0	D
REVEL	Uncertain	0.34
Sift	Uncertain	0.0020	D
Sift4G	Benign	0.069	T
Vest4		0.80
MutPred		0.67		Loss of MoRF binding (P = 0.0283)
MVP		0.41
ClinPred		0.25	T
GERP RS		2.3
Varity_R		0.51
gMVP		0.034
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: rs751844623; hg19: chr2-88082222;