chr1-17438276-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018715.4(RCC2):​c.239G>A​(p.Gly80Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000172 in 1,159,490 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 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. G80C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)
Exomes 𝑓: 0.0000017 ( 0 hom. )

Consequence

RCC2
NM_018715.4 missense

Scores

2
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.80
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.17674747).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
RCC2NM_018715.4 linkc.239G>A p.Gly80Asp missense_variant Exon 2 of 13 ENST00000375436.9 NP_061185.1 Q9P258A0A024RAC5
RCC2NM_001136204.3 linkc.239G>A p.Gly80Asp missense_variant Exon 1 of 12 NP_001129676.1 Q9P258A0A024RAC5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
RCC2ENST00000375436.9 linkc.239G>A p.Gly80Asp missense_variant Exon 2 of 13 1 NM_018715.4 ENSP00000364585.4 Q9P258
RCC2ENST00000375433.3 linkc.239G>A p.Gly80Asp missense_variant Exon 1 of 12 1 ENSP00000364582.3 Q9P258

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
0.00000172
AC:
2
AN:
1159490
Hom.:
0
Cov.:
30
AF XY:
0.00
AC XY:
0
AN XY:
572274
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000191
Gnomad4 FIN exome
AF:
0.0000269
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Feb 06, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.239G>A (p.G80D) alteration is located in exon 2 (coding exon 1) of the RCC2 gene. This alteration results from a G to A substitution at nucleotide position 239, causing the glycine (G) at amino acid position 80 to be replaced by an aspartic acid (D). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
18
DANN
Benign
0.95
DEOGEN2
Benign
0.021
T;T
Eigen
Benign
-0.64
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.038
N
M_CAP
Pathogenic
0.30
D
MetaRNN
Benign
0.18
T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.60
N;N
PrimateAI
Pathogenic
0.83
D
PROVEAN
Benign
0.69
N;N
REVEL
Benign
0.066
Sift
Benign
0.60
T;T
Sift4G
Benign
0.72
T;T
Polyphen
0.92
P;P
Vest4
0.22
MutPred
0.36
Gain of ubiquitination at K77 (P = 0.0453);Gain of ubiquitination at K77 (P = 0.0453);
MVP
0.082
MPC
1.1
ClinPred
0.19
T
GERP RS
1.6
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
2.6
Varity_R
0.071
gMVP
0.24

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-17764772; API