Genetic Variant RCC2:p.Gly66Asp (chr1-17438318-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018715.4(RCC2):c.197G>A(p.Gly66Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G66C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

RCC2
NM_018715.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.350

Publications

0 publications found

Variant links:

Genes affected

RCC2 (HGNC:30297): (regulator of chromosome condensation 2) The protein encoded by this gene is a guanine exchange factor that is active on RalA, a small GTPase. The encoded protein and RalA are both essential for proper kinetochore-microtubule function in early mitosis. This protein has been shown to be a biomarker for colorectal cancer. [provided by RefSeq, Oct 2016]

RCC2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.10881394).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018715.4. 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
	RCC2	NM_018715.4	MANE Select	c.197G>A	p.Gly66Asp	missense	Exon 2 of 13	NP_061185.1	A0A024RAC5
	RCC2	NM_001136204.3		c.197G>A	p.Gly66Asp	missense	Exon 1 of 12	NP_001129676.1	Q9P258

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
RCC2	ENST00000375436.9	TSL:1 MANE Select	c.197G>A	p.Gly66Asp	missense	Exon 2 of 13	ENSP00000364585.4	Q9P258
RCC2	ENST00000375433.3	TSL:1	c.197G>A	p.Gly66Asp	missense	Exon 1 of 12	ENSP00000364582.3	Q9P258
RCC2	ENST00000927104.1		c.197G>A	p.Gly66Asp	missense	Exon 1 of 12	ENSP00000597163.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1089626

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

528500

African (AFR)

AF:

0.00

AC:

AN:

21156

American (AMR)

AF:

0.00

AC:

AN:

7598

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

12270

East Asian (EAS)

AF:

0.00

AC:

AN:

19814

South Asian (SAS)

AF:

0.00

AC:

AN:

34310

European-Finnish (FIN)

AF:

0.00

AC:

AN:

32448

Middle Eastern (MID)

AF:

0.00

AC:

AN:

2744

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

918144

Other (OTH)

AF:

0.00

AC:

AN:

41142

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.22

BayesDel_addAF

Benign

-0.21

BayesDel_noAF

Benign

-0.54

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.023

Eigen

Benign

-0.59

Eigen_PC

Benign

-0.50

FATHMM_MKL

Benign

0.10

M_CAP

Pathogenic

0.37

MetaRNN

Benign

0.11

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

PhyloP100

0.35

PrimateAI

Pathogenic

0.85

PROVEAN

Benign

0.020

REVEL

Benign

0.032

Sift

Benign

0.38

Sift4G

Uncertain

0.055

Polyphen

0.32

Vest4

0.20

MutPred

0.29

Loss of MoRF binding (P = 0.0385)

MVP

0.28

MPC

1.1

ClinPred

0.13

GERP RS

1.5

PromoterAI

0.060

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.077

gMVP

0.37

Mutation Taster

=76/24

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

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

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over