rs10498767

Positions:

• chr6-46395820-C-G
• chr6-46395820-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001251974.2(RCAN2):​c.225+60932G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.5 in 151,936 control chromosomes in the GnomAD database, including 19,667 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 0.50 (19667 hom., cov: 31)
• Consequence: RCAN2 NM_001251974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0800

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.592 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.225+60932G>C		intron_variant		ENST00000371374.6	NP_001238903.1
RCAN2	NM_001251973.2	c.225+60932G>C		intron_variant			NP_001238902.1
RCAN2	XM_011514226.2	c.225+60932G>C		intron_variant			XP_011512528.1
RCAN2	XM_024446301.2	c.225+60932G>C		intron_variant			XP_024302069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RCAN2	ENST00000371374.6	c.225+60932G>C		intron_variant		1	NM_001251974.2	ENSP00000360425
RCAN2	ENST00000306764.11	c.225+60932G>C		intron_variant		1		ENSP00000305223

Frequencies

GnomAD3 genomes AF: 0.500 AC: 75851 AN: 151818 Hom.: 19637 Cov.: 31

Gnomad AFR AF: 0.362

Gnomad AMI AF: 0.618

Gnomad AMR AF: 0.506

Gnomad ASJ AF: 0.412

Gnomad EAS AF: 0.610

Gnomad SAS AF: 0.609

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.392

Gnomad NFE AF: 0.548

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.500 AC: 75937 AN: 151936 Hom.: 19667 Cov.: 31 AF XY: 0.505 AC XY: 37521 AN XY: 74264

Gnomad4 AFR AF: 0.362

Gnomad4 AMR AF: 0.506

Gnomad4 ASJ AF: 0.412

Gnomad4 EAS AF: 0.610

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.548

Gnomad4 OTH AF: 0.503

Alfa AF: 0.431 Hom.: 1355

Bravo AF: 0.483

Asia WGS AF: 0.618 AC: 2144 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	2.8
DANN	Benign	0.33

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10498767; hg19: chr6-46363557;