rs10498767

Variant names:

• chr6-46395820-C-G
• rs10498767
• NM_001251974.2:c.225+60932G>C

Your query was ambiguous. Multiple possible variants found:

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

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+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
• Publications: 5 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]

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.225+60932G>C		intron_variant	Intron 2 of 4	ENST00000371374.6	NP_001238903.1
RCAN2	NM_001251973.2	c.225+60932G>C		intron_variant	Intron 2 of 4		NP_001238902.1
RCAN2	XM_011514226.2	c.225+60932G>C		intron_variant	Intron 2 of 4		XP_011512528.1
RCAN2	XM_024446301.2	c.225+60932G>C		intron_variant	Intron 2 of 4		XP_024302069.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCAN2	ENST00000371374.6	c.225+60932G>C		intron_variant	Intron 2 of 4	1	NM_001251974.2	ENSP00000360425.1
RCAN2	ENST00000306764.11	c.225+60932G>C		intron_variant	Intron 2 of 4	1		ENSP00000305223.7

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

African (AFR) AF: 0.362 AC: 15011 AN: 41430

American (AMR) AF: 0.506 AC: 7728 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.412 AC: 1431 AN: 3470

East Asian (EAS) AF: 0.610 AC: 3140 AN: 5148

South Asian (SAS) AF: 0.608 AC: 2922 AN: 4802

European-Finnish (FIN) AF: 0.635 AC: 6697 AN: 10554

Middle Eastern (MID) AF: 0.395 AC: 116 AN: 294

European-Non Finnish (NFE) AF: 0.548 AC: 37269 AN: 67958

Other (OTH) AF: 0.503 AC: 1061 AN: 2108

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
PhyloP100		0.080
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: rs10498767; hg19: chr6-46363557;