chr1-17438484-A-G
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Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP4BS2
The NM_018715.4(RCC2):āc.31T>Cā(p.Trp11Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000118 in 1,341,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.000073 ( 0 hom., cov: 32)
Exomes š: 0.00012 ( 1 hom. )
Consequence
RCC2
NM_018715.4 missense
NM_018715.4 missense
Scores
5
13
Clinical Significance
Conservation
PhyloP100: 1.04
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 -5 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.27060384).
BS2
High AC in GnomAd4 at 11 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCC2 | NM_018715.4 | c.31T>C | p.Trp11Arg | missense_variant | 2/13 | ENST00000375436.9 | |
RCC2 | NM_001136204.3 | c.31T>C | p.Trp11Arg | missense_variant | 1/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCC2 | ENST00000375436.9 | c.31T>C | p.Trp11Arg | missense_variant | 2/13 | 1 | NM_018715.4 | P1 | |
RCC2 | ENST00000375433.3 | c.31T>C | p.Trp11Arg | missense_variant | 1/12 | 1 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000726 AC: 11AN: 151458Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.000123 AC: 147AN: 1190382Hom.: 1 Cov.: 30 AF XY: 0.000116 AC XY: 67AN XY: 579170
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GnomAD4 genome AF: 0.0000726 AC: 11AN: 151458Hom.: 0 Cov.: 32 AF XY: 0.0000541 AC XY: 4AN XY: 73942
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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 | Mar 29, 2023 | The c.31T>C (p.W11R) alteration is located in exon 2 (coding exon 1) of the RCC2 gene. This alteration results from a T to C substitution at nucleotide position 31, causing the tryptophan (W) at amino acid position 11 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Uncertain
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
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
Pathogenic
D;D
Sift4G
Pathogenic
D;D
Polyphen
P;P
Vest4
MutPred
Gain of methylation at W11 (P = 0.0125);Gain of methylation at W11 (P = 0.0125);
MVP
MPC
ClinPred
T
GERP RS
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