dbSNP rs10498766: RCAN2:c.225+95692A>C (chr6-46361060-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is . The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_001251974.2(RCAN2):c.225+95692A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.444 in 151,760 control chromosomes in the GnomAD database, including 16,448 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.44 ( 16448 hom., cov: 32)

Consequence

RCAN2
NM_001251974.2 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.180

Publications

0 publications found

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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new If you want to explore the variant's impact on the transcript NM_001251974.2, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251974.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
RCAN2	NM_001251974.2	MANE Select	c.225+95692A>C	intron	N/A	NP_001238903.1	Q14206-2
RCAN2	NM_001251973.2		c.225+95692A>C	intron	N/A	NP_001238902.1	Q14206-2
LOC101926915	NR_125838.1		n.286-51T>G	intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCAN2	ENST00000371374.6	TSL:1 MANE Select	c.225+95692A>C		intron	N/A	ENSP00000360425.1	Q14206-2
	RCAN2	ENST00000306764.11	TSL:1	c.225+95692A>C		intron	N/A	ENSP00000305223.7	Q14206-2

Frequencies

GnomAD3 genomes

AF:

0.444

AC:

67319

AN:

151642

Hom.:

16438

Cov.:

show subpopulations

Gnomad AFR

AF:

0.225

Gnomad AMI

AF:

0.541

Gnomad AMR

AF:

0.476

Gnomad ASJ

AF:

0.390

Gnomad EAS

AF:

0.597

Gnomad SAS

AF:

0.438

Gnomad FIN

AF:

0.624

Gnomad MID

AF:

0.357

Gnomad NFE

AF:

0.533

Gnomad OTH

AF:

0.449

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.444

AC:

67349

AN:

151760

Hom.:

16448

Cov.:

AF XY:

0.447

AC XY:

33157

AN XY:

74134

show subpopulations

African (AFR)

AF:

0.225

AC:

9324

AN:

41474

American (AMR)

AF:

0.476

AC:

7268

AN:

15260

Ashkenazi Jewish (ASJ)

AF:

0.390

AC:

1354

AN:

3470

East Asian (EAS)

AF:

0.598

AC:

3064

AN:

5128

South Asian (SAS)

AF:

0.438

AC:

2110

AN:

4814

European-Finnish (FIN)

AF:

0.624

AC:

6529

AN:

10468

Middle Eastern (MID)

AF:

0.356

AC:

104

AN:

292

European-Non Finnish (NFE)

AF:

0.533

AC:

36154

AN:

67842

Other (OTH)

AF:

0.452

AC:

953

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

1803

3606

5410

7213

9016

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

624

1248

1872

2496

3120

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.492

Hom.:

2336

Bravo

AF:

0.425

Asia WGS

AF:

0.511

AC:

1774

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

(source)

DANN

Benign

0.82

PhyloP100

0.18

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over