chr1-17425679-A-G
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_018715.4(RCC2):c.385T>C(p.Tyr129His) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000206 in 1,457,404 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: not found (cov: 33)
Exomes 𝑓: 0.0000021 ( 0 hom. )
Consequence
RCC2
NM_018715.4 missense
NM_018715.4 missense
Scores
3
4
11
Clinical Significance
Conservation
PhyloP100: 9.23
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 Uncertain_significance. Variant got 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.3499196).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCC2 | NM_018715.4 | c.385T>C | p.Tyr129His | missense_variant | 4/13 | ENST00000375436.9 | |
RCC2 | NM_001136204.3 | c.385T>C | p.Tyr129His | missense_variant | 3/12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCC2 | ENST00000375436.9 | c.385T>C | p.Tyr129His | missense_variant | 4/13 | 1 | NM_018715.4 | P1 | |
RCC2 | ENST00000375433.3 | c.385T>C | p.Tyr129His | missense_variant | 3/12 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD3 exomes AF: 0.0000121 AC: 3AN: 248852Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 134922
GnomAD3 exomes
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GnomAD4 exome AF: 0.00000206 AC: 3AN: 1457404Hom.: 0 Cov.: 32 AF XY: 0.00000276 AC XY: 2AN XY: 724086
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GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ExAC
?
AF:
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2
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 | Jan 19, 2022 | The c.385T>C (p.Y129H) alteration is located in exon 4 (coding exon 3) of the RCC2 gene. This alteration results from a T to C substitution at nucleotide position 385, causing the tyrosine (Y) at amino acid position 129 to be replaced by a histidine (H). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Uncertain
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;M
MutationTaster
Benign
D;D
PrimateAI
Pathogenic
D
PROVEAN
Benign
N;N
REVEL
Benign
Sift
Benign
T;T
Sift4G
Benign
T;T
Polyphen
D;D
Vest4
MutPred
Gain of disorder (P = 0.0233);Gain of disorder (P = 0.0233);
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Score
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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