Variant 6-46456965-T-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001251974.2(RCAN2):c.12A>C(p.Glu4Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0067 in 1,549,912 control chromosomes in the GnomAD database, including 49 homozygotes. In-silico tool predicts a benign outcome for this variant. 11/16 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.0048 ( 6 hom., cov: 32)

Exomes 𝑓: 0.0069 ( 43 hom. )

Consequence

RCAN2
NM_001251974.2 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.141

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.00451687).

BP6

Variant 6-46456965-T-G is Benign according to our data. Variant chr6-46456965-T-G is described in ClinVar as [Benign]. Clinvar id is 2656618.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAd4 at 6 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
RCAN2	NM_001251974.2 linkuse as main transcript	c.12A>C	p.Glu4Asp	missense_variant	2/5	ENST00000371374.6	NP_001238903.1
RCAN2	NM_001251973.2 linkuse as main transcript	c.12A>C	p.Glu4Asp	missense_variant	2/5		NP_001238902.1
RCAN2	XM_011514226.2 linkuse as main transcript	c.12A>C	p.Glu4Asp	missense_variant	2/5		XP_011512528.1
RCAN2	XM_024446301.2 linkuse as main transcript	c.12A>C	p.Glu4Asp	missense_variant	2/5		XP_024302069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCAN2	ENST00000371374.6 linkuse as main transcript	c.12A>C	p.Glu4Asp	missense_variant	2/5	1	NM_001251974.2	ENSP00000360425		Q14206-2
RCAN2	ENST00000306764.11 linkuse as main transcript	c.12A>C	p.Glu4Asp	missense_variant	2/5	1		ENSP00000305223		Q14206-2

Frequencies

GnomAD3 genomes

AF:

0.00478

AC:

728

AN:

152214

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00118

Gnomad AMI

AF:

0.0263

Gnomad AMR

AF:

0.00353

Gnomad ASJ

AF:

0.0179

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00188

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00732

Gnomad OTH

AF:

0.00860

GnomAD3 exomes

AF:

0.00436

AC:

655

AN:

150390

Hom.:

AF XY:

0.00431

AC XY:

347

AN XY:

80568

show subpopulations

Gnomad AFR exome

AF:

0.000991

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.0202

Gnomad EAS exome

AF:

0.000185

Gnomad SAS exome

AF:

0.00111

Gnomad FIN exome

AF:

0.000944

Gnomad NFE exome

AF:

0.00655

Gnomad OTH exome

AF:

0.00366

GnomAD4 exome

AF:

0.00691

AC:

9653

AN:

1397580

Hom.:

Cov.:

AF XY:

0.00676

AC XY:

4662

AN XY:

689396

show subpopulations

Gnomad4 AFR exome

AF:

0.00136

Gnomad4 AMR exome

AF:

0.00241

Gnomad4 ASJ exome

AF:

0.0193

Gnomad4 EAS exome

AF:

0.0000840

Gnomad4 SAS exome

AF:

0.00115

Gnomad4 FIN exome

AF:

0.00103

Gnomad4 NFE exome

AF:

0.00787

Gnomad4 OTH exome

AF:

0.00696

GnomAD4 genome

AF:

0.00478

AC:

728

AN:

152332

Hom.:

Cov.:

AF XY:

0.00422

AC XY:

314

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00118

Gnomad4 AMR

AF:

0.00353

Gnomad4 ASJ

AF:

0.0179

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000414

Gnomad4 FIN

AF:

0.00188

Gnomad4 NFE

AF:

0.00732

Gnomad4 OTH

AF:

0.00851

Alfa

AF:

0.00652

Hom.:

Bravo

AF:

0.00492

TwinsUK

AF:

0.00701

AC:

ALSPAC

AF:

0.00752

AC:

ExAC

AF:

0.00329

AC:

Asia WGS

AF:

0.000866

AC:

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

RCAN2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Uncertain

0.99

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.54

LIST_S2

Benign

0.61

.;T

M_CAP

Benign

0.0046

MetaRNN

Benign

0.0045

T;T

MetaSVM

Benign

-1.0

MutationTaster

Benign

0.97

N;N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

-0.14

N;N

REVEL

Benign

0.047

Sift

Benign

0.44

T;T

Sift4G

Benign

1.0

T;T

Polyphen

0.0

B;B

Vest4

0.11

MutPred

0.18

Loss of sheet (P = 0.0228);Loss of sheet (P = 0.0228);

MVP

0.53

MPC

0.62

ClinPred

0.0035

GERP RS

-1.4

gMVP

0.53

Splicing

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