NM_001078170.3:c.4355T>A

Variant names:

• chr2-87782669-A-T
• rs764274376
• NM_001078170.3:c.4355T>A

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP4_Moderate

The NM_001078170.3(RGPD2):​c.4355T>A​(p.Ile1452Asn) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000099 (0 hom., cov: 5)
  • Exomes 𝑓: 0.00015 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD2 NM_001078170.3 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.23
• 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 -2 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.14524037).

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.4355T>A	p.Ile1452Asn	missense	Exon 20 of 23	NP_001071638.2	P0DJD1
	RGPD2	NM_001393613.1		c.4196T>A	p.Ile1399Asn	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.4355T>A	p.Ile1452Asn	missense	Exon 20 of 23	ENSP00000381214.3	P0DJD1
	RGPD2	ENST00000494592.1	TSL:1	n.1T>A		non_coding_transcript_exon	Exon 1 of 2
	RGPD2	ENST00000971290.1		c.4352T>A	p.Ile1451Asn	missense	Exon 20 of 23	ENSP00000641349.1

Frequencies

GnomAD3 genomes AF: 0.0000987 AC: 2 AN: 20258 Hom.: 0 Cov.: 5

Gnomad AFR AF: 0.000107

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: 0.000687

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000378 AC: 2 AN: 52894 AF XY: 0.0000376

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.000711

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000488

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000146 AC: 102 AN: 700802 Hom.: 1 Cov.: 9 AF XY: 0.000146 AC XY: 52 AN XY: 357072

African (AFR) AF: 0.00 AC: 0 AN: 20938

American (AMR) AF: 0.00 AC: 0 AN: 19600

Ashkenazi Jewish (ASJ) AF: 0.00195 AC: 30 AN: 15412

East Asian (EAS) AF: 0.00 AC: 0 AN: 32250

South Asian (SAS) AF: 0.00 AC: 0 AN: 50734

European-Finnish (FIN) AF: 0.000197 AC: 6 AN: 30472

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2510

European-Non Finnish (NFE) AF: 0.000119 AC: 59 AN: 494588

Other (OTH) AF: 0.000204 AC: 7 AN: 34298

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000987 AC: 2 AN: 20258 Hom.: 0 Cov.: 5 AF XY: 0.000106 AC XY: 1 AN XY: 9422

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

African (AFR) AF: 0.000107 AC: 1 AN: 9360

American (AMR) AF: 0.00 AC: 0 AN: 1680

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 282

East Asian (EAS) AF: 0.00 AC: 0 AN: 480

South Asian (SAS) AF: 0.00 AC: 0 AN: 334

European-Finnish (FIN) AF: 0.000687 AC: 1 AN: 1456

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 90

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6224

Other (OTH) AF: 0.00 AC: 0 AN: 254

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0.0385499), which strongly suggests a high chance of mosaicism in these individuals.

Alfa AF: 0.0000744 Hom.: 0

ExAC AF: 0.0000674 AC: 3

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	0.32
BayesDel_addAF	Benign	-0.14	T
BayesDel_noAF	Benign	-0.44
CADD	Uncertain	23
DANN	Uncertain	0.98
DEOGEN2	Benign	0.078	T
Eigen	Benign	-0.11
Eigen_PC	Benign	-0.15
FATHMM_MKL	Benign	0.71	D
LIST_S2	Uncertain	0.88	D
M_CAP	Benign	0.014	T
MetaRNN	Benign	0.15	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
PhyloP100		3.2
PrimateAI	Uncertain	0.69	T
PROVEAN	Uncertain	-3.4	D
REVEL	Benign	0.15
Sift	Benign	0.26	T
Sift4G	Benign	0.10	T
Vest4		0.68
MutPred		0.60		Gain of disorder (P = 0.0268)
MVP		0.36
ClinPred		0.33	T
GERP RS		2.3
Varity_R		0.34
gMVP		0.032
Mutation Taster		=90/10	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: rs764274376; hg19: chr2-88082188;