rs10498766

Variant names:

• chr6-46361060-T-G
• rs10498766
• NM_001251974.2:c.225+95692A>C

Variant summary

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

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.180
• Publications: 0 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]

LOC101926915 (HGNC:):

ACMG classification

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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.225+95692A>C		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.225+95692A>C		intron_variant	Intron 2 of 4	1	NM_001251974.2	ENSP00000360425.1
RCAN2	ENST00000306764.11	c.225+95692A>C		intron_variant	Intron 2 of 4	1		ENSP00000305223.7

Frequencies

GnomAD3 genomes AF: 0.444 AC: 67319 AN: 151642 Hom.: 16438 Cov.: 32

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.: 32 AF XY: 0.447 AC XY: 33157 AN XY: 74134

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

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 v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	13
DANN	Benign	0.82
PhyloP100		0.18
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: rs10498766; hg19: chr6-46328797;