Variant chr6-46325463-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_005822.4(RCAN2):c.17T>G(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: 𝑓 0.0000066 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0000048 ( 0 hom. )

Consequence

RCAN2
NM_005822.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.48

Variant links:

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]

RCAN2 links:

LOC101926915 (HGNC:):

LOC101926915 links:

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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 linkuse as main transcript	c.226-76567T>G		intron_variant		ENST00000371374.6	NP_001238903.1	Q14206-2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	UniProt
RCAN2	ENST00000330430.10 linkuse as main transcript	c.17T>G	p.Met6Arg	missense_variant	1/4	1		ENSP00000329454.6	Q14206-1
RCAN2	ENST00000371374.6 linkuse as main transcript	c.226-76567T>G		intron_variant		1	NM_001251974.2	ENSP00000360425.1	Q14206-2
RCAN2	ENST00000306764.11 linkuse as main transcript	c.226-76567T>G		intron_variant		1		ENSP00000305223.7	Q14206-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249402

Hom.:

AF XY:

0.00000739

AC XY:

AN XY:

135326

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000883

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000479

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.00000825

AC XY:

AN XY:

727194

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000630

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152260

Hom.:

Cov.:

AF XY:

0.0000134

AC XY:

AN XY:

74394

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000827

AC:

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: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.17

BayesDel_addAF

Pathogenic

0.35

BayesDel_noAF

Pathogenic

0.28

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.19

T;T

Eigen

Uncertain

0.41

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.72

T;T

M_CAP

Benign

0.011

MetaRNN

Uncertain

0.51

D;D

MetaSVM

Benign

-0.89

MutationAssessor

Benign

1.2

L;.

PROVEAN

Benign

-0.81

N;.

REVEL

Benign

0.25

Sift

Uncertain

0.0070

D;.

Sift4G

Benign

0.37

T;T

Polyphen

0.68

P;.

Vest4

0.77

MutPred

0.24

Gain of solvent accessibility (P = 0.039);Gain of solvent accessibility (P = 0.039);

MVP

0.73

ClinPred

0.40

GERP RS

5.3

Varity_R

0.79

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over