6-46337717-T-C

Variant names:

• chr6-46337717-T-C
• rs1372568
• NM_001251974.2:c.226-88821A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251974.2(RCAN2):​c.226-88821A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.425 in 152,008 control chromosomes in the GnomAD database, including 15,072 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 0.43 (15072 hom., cov: 32)
• Consequence: RCAN2 NM_001251974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.00900
• Publications: 1 publications found

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]

ENSG00000307576 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.584 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.226-88821A>G		intron_variant	Intron 2 of 4	ENST00000371374.6	NP_001238903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCAN2	ENST00000371374.6	c.226-88821A>G		intron_variant	Intron 2 of 4	1	NM_001251974.2	ENSP00000360425.1

Frequencies

GnomAD3 genomes AF: 0.425 AC: 64572 AN: 151890 Hom.: 15061 Cov.: 32

Gnomad AFR AF: 0.218

Gnomad AMI AF: 0.428

Gnomad AMR AF: 0.464

Gnomad ASJ AF: 0.380

Gnomad EAS AF: 0.602

Gnomad SAS AF: 0.428

Gnomad FIN AF: 0.601

Gnomad MID AF: 0.345

Gnomad NFE AF: 0.504

Gnomad OTH AF: 0.432

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

GnomAD4 genome AF: 0.425 AC: 64607 AN: 152008 Hom.: 15072 Cov.: 32 AF XY: 0.430 AC XY: 31940 AN XY: 74288

African (AFR) AF: 0.217 AC: 9017 AN: 41476

American (AMR) AF: 0.464 AC: 7085 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.380 AC: 1318 AN: 3468

East Asian (EAS) AF: 0.602 AC: 3110 AN: 5170

South Asian (SAS) AF: 0.429 AC: 2068 AN: 4818

European-Finnish (FIN) AF: 0.601 AC: 6348 AN: 10558

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.504 AC: 34252 AN: 67934

Other (OTH) AF: 0.436 AC: 920 AN: 2110

Alfa AF: 0.460 Hom.: 2210

Bravo AF: 0.407

Asia WGS AF: 0.503 AC: 1748 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	7.6
DANN	Benign	0.38
PhyloP100		0.0090
Mutation Taster		=100/0	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs1372568; hg19: chr6-46305454;