2-112378247-T-C

Variant names:

• chr2-112378247-T-C
• rs768043259
• NM_001164463.1:c.5069A>G

Variant summary

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

The NM_001164463.1(RGPD8):​c.5069A>G​(p.Lys1690Arg) variant causes a missense change. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.021 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: RGPD8 NM_001164463.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.89
• Publications: 1 publications found

Genes affected

RGPD8 (HGNC:9849): (RANBP2 like and GRIP domain containing 8) 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 0 ACMG points.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001164463.1. 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
	RGPD8	NM_001164463.1	MANE Select	c.5069A>G	p.Lys1690Arg	missense	Exon 22 of 23	NP_001157935.1	O14715

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RGPD8	ENST00000302558.8	TSL:1 MANE Select	c.5069A>G	p.Lys1690Arg	missense	Exon 22 of 23	ENSP00000306637.3	O14715
	RGPD8	ENST00000409750.5	TSL:1	c.4649A>G	p.Lys1550Arg	missense	Exon 21 of 22	ENSP00000386511.1	J3KQ37
	RGPD8	ENST00000929966.1		c.3032A>G	p.Lys1011Arg	missense	Exon 9 of 10	ENSP00000600025.1

Frequencies

GnomAD3 genomes AF: 0.0161 AC: 2 AN: 124 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMR AF: 0.0625

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.0385

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0209 AC: 1650 AN: 78866 Hom.: 1 Cov.: 0 AF XY: 0.0220 AC XY: 919 AN XY: 41698

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

African (AFR) AF: 0.00371 AC: 11 AN: 2964

American (AMR) AF: 0.0644 AC: 242 AN: 3758

Ashkenazi Jewish (ASJ) AF: 0.0313 AC: 53 AN: 1694

East Asian (EAS) AF: 0.0593 AC: 293 AN: 4938

South Asian (SAS) AF: 0.0399 AC: 444 AN: 11138

European-Finnish (FIN) AF: 0.0116 AC: 29 AN: 2492

Middle Eastern (MID) AF: 0.0120 AC: 3 AN: 250

European-Non Finnish (NFE) AF: 0.0103 AC: 494 AN: 47792

Other (OTH) AF: 0.0211 AC: 81 AN: 3840

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0154 AC: 2 AN: 130 Hom.: 0 Cov.: 0 AF XY: 0.0167 AC XY: 1 AN XY: 60

⚠️ 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: 30

American (AMR) AF: 0.0625 AC: 1 AN: 16

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 4

East Asian (EAS) AF: 0.0385 AC: 1 AN: 26

South Asian (SAS) AF: 0.00 AC: 0 AN: 4

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 6

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 42

Other (OTH) AF: 0.00 AC: 0 AN: 2

⚠️ 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: 0.00632 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	0.096
BayesDel_addAF	Benign	-0.080	T
BayesDel_noAF	Benign	-0.35
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.0046	T
Eigen	Benign	0.027
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.73	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.0037	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	1.8	L
PhyloP100		5.9
PrimateAI	Uncertain	0.70	T
PROVEAN	Benign	-0.40	N
REVEL	Benign	0.21
Sift	Pathogenic	0.0	D
Sift4G	Uncertain	0.034	D
Polyphen		0.98	D
Vest4		0.14
MutPred		0.23		Gain of MoRF binding (P = 0.0798)
MVP		0.030
ClinPred		0.85	D
GERP RS		0.86
Varity_R		0.23
gMVP		0.062
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.21		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.21		Position offset: -1

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs768043259; hg19: chr2-113135824;