6-46325463-A-C
Position:
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_005822.4(RCAN2):āc.17T>Gā(p.Met6Arg) variant causes a missense change. The variant allele was found at a frequency of 0.00000496 in 1,614,068 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 33)
Exomes š: 0.0000048 ( 0 hom. )
Consequence
RCAN2
NM_005822.4 missense
NM_005822.4 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: 6.48
Genes affected
RCAN2 (HGNC:3041): (regulator of calcineurin 2) This gene encodes a member of the regulator of calcineurin (RCAN) protein family. These proteins play a role in many physiological processes by binding to the catalytic domain of calcineurin A, inhibiting calcineurin-mediated nuclear translocation of the transcription factor NFATC1. Expression of this gene in skin fibroblasts is upregulated by thyroid hormone, and the encoded protein may also play a role in endothelial cell function and angiogenesis. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene. [provided by RefSeq, Oct 2011]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 2 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
RCAN2 | NM_001251974.2 | c.226-76567T>G | intron_variant | ENST00000371374.6 | NP_001238903.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
RCAN2 | ENST00000330430.10 | c.17T>G | p.Met6Arg | missense_variant | 1/4 | 1 | ENSP00000329454.6 | |||
RCAN2 | ENST00000371374.6 | c.226-76567T>G | intron_variant | 1 | NM_001251974.2 | ENSP00000360425.1 | ||||
RCAN2 | ENST00000306764.11 | c.226-76567T>G | intron_variant | 1 | ENSP00000305223.7 |
Frequencies
GnomAD3 genomes AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 33
GnomAD3 genomes
AF:
AC:
1
AN:
152260
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000401 AC: 1AN: 249402Hom.: 0 AF XY: 0.00000739 AC XY: 1AN XY: 135326
GnomAD3 exomes
AF:
AC:
1
AN:
249402
Hom.:
AF XY:
AC XY:
1
AN XY:
135326
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00000479 AC: 7AN: 1461808Hom.: 0 Cov.: 30 AF XY: 0.00000825 AC XY: 6AN XY: 727194
GnomAD4 exome
AF:
AC:
7
AN:
1461808
Hom.:
Cov.:
30
AF XY:
AC XY:
6
AN XY:
727194
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00000657 AC: 1AN: 152260Hom.: 0 Cov.: 33 AF XY: 0.0000134 AC XY: 1AN XY: 74394
GnomAD4 genome
AF:
AC:
1
AN:
152260
Hom.:
Cov.:
33
AF XY:
AC XY:
1
AN XY:
74394
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
ExAC
AF:
AC:
1
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 | Sep 11, 2024 | The c.17T>G (p.M6R) alteration is located in exon 1 (coding exon 1) of the RCAN2 gene. This alteration results from a T to G substitution at nucleotide position 17, causing the methionine (M) at amino acid position 6 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
Benign
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Pathogenic
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Uncertain
D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Uncertain
D;.
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);
MVP
ClinPred
T
GERP RS
Varity_R
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at