15-76943762-A-G
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Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4
The NM_002902.3(RCN2):āc.452A>Gā(p.His151Arg) variant causes a missense change. The variant allele was found at a frequency of 0.0000596 in 1,577,330 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 (ā ).
Frequency
Genomes: š 0.000026 ( 0 hom., cov: 32)
Exomes š: 0.000063 ( 0 hom. )
Consequence
RCN2
NM_002902.3 missense
NM_002902.3 missense
Scores
11
8
Clinical Significance
Conservation
PhyloP100: 5.48
Genes affected
RCN2 (HGNC:9935): (reticulocalbin 2) The protein encoded by this gene is a calcium-binding protein located in the lumen of the ER. The protein contains six conserved regions with similarity to a high affinity Ca(+2)-binding motif, the EF-hand. This gene maps to the same region as type 4 Bardet-Biedl syndrome, suggesting a possible causative role for this gene in the disorder. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2012]
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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=0.3243745).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RCN2 | NM_002902.3 | c.452A>G | p.His151Arg | missense_variant | 4/7 | ENST00000394885.8 | |
RCN2 | NM_001271837.2 | c.506A>G | p.His169Arg | missense_variant | 5/8 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
RCN2 | ENST00000394885.8 | c.452A>G | p.His151Arg | missense_variant | 4/7 | 1 | NM_002902.3 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000263 AC: 4AN: 152174Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000106 AC: 26AN: 245550Hom.: 0 AF XY: 0.000151 AC XY: 20AN XY: 132602
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GnomAD4 exome AF: 0.0000632 AC: 90AN: 1425038Hom.: 0 Cov.: 27 AF XY: 0.0000930 AC XY: 66AN XY: 709678
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GnomAD4 genome AF: 0.0000263 AC: 4AN: 152292Hom.: 0 Cov.: 32 AF XY: 0.0000403 AC XY: 3AN XY: 74472
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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 | Nov 09, 2021 | The c.452A>G (p.H151R) alteration is located in exon 4 (coding exon 4) of the RCN2 gene. This alteration results from a A to G substitution at nucleotide position 452, causing the histidine (H) at amino acid position 151 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;.;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Uncertain
D;T;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T
MetaSVM
Benign
T
MutationAssessor
Uncertain
M;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;N;N
REVEL
Benign
Sift
Uncertain
D;D;T
Sift4G
Benign
T;T;T
Polyphen
D;.;P
Vest4
MutPred
Loss of helix (P = 0.0104);.;.;
MVP
MPC
ClinPred
T
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