1-17438319-C-A
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BP4_Strong
The NM_018715.4(RCC2):c.196G>T(p.Gly66Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000887 in 1,239,958 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000073 ( 0 hom. )
Consequence
RCC2
NM_018715.4 missense
NM_018715.4 missense
Scores
2
3
13
Clinical Significance
Conservation
PhyloP100: 1.44
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]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.026974052).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCC2 | NM_018715.4 | c.196G>T | p.Gly66Cys | missense_variant | 2/13 | ENST00000375436.9 | |
RCC2 | NM_001136204.3 | c.196G>T | p.Gly66Cys | missense_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCC2 | ENST00000375436.9 | c.196G>T | p.Gly66Cys | missense_variant | 2/13 | 1 | NM_018715.4 | P1 | |
RCC2 | ENST00000375433.3 | c.196G>T | p.Gly66Cys | missense_variant | 1/12 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000201 AC: 3AN: 149460Hom.: 0 Cov.: 32
GnomAD3 genomes
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GnomAD4 exome AF: 0.00000734 AC: 8AN: 1090498Hom.: 0 Cov.: 30 AF XY: 0.00000567 AC XY: 3AN XY: 528852
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GnomAD4 genome ? AF: 0.0000201 AC: 3AN: 149460Hom.: 0 Cov.: 32 AF XY: 0.0000412 AC XY: 3AN XY: 72890
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | May 05, 2023 | The c.196G>T (p.G66C) alteration is located in exon 2 (coding exon 1) of the RCC2 gene. This alteration results from a G to T substitution at nucleotide position 196, causing the glycine (G) at amino acid position 66 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
N;N
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Uncertain
D;D
Sift4G
Uncertain
D;D
Polyphen
D;D
Vest4
MutPred
Gain of methylation at K67 (P = 0.0259);Gain of methylation at K67 (P = 0.0259);
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at