NM_001251974.2:c.225+62411C>A

Variant names:

• chr6-46394341-G-T
• rs953887
• NM_001251974.2:c.225+62411C>A

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+62411C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.408 in 152,054 control chromosomes in the GnomAD database, including 15,621 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 0.41 (15621 hom., cov: 33)
• Consequence: RCAN2 NM_001251974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.498
• Publications: 2 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=-0.79).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.577 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.225+62411C>A		intron_variant	Intron 2 of 4	ENST00000371374.6	NP_001238903.1
RCAN2	NM_001251973.2	c.225+62411C>A		intron_variant	Intron 2 of 4		NP_001238902.1
RCAN2	XM_011514226.2	c.225+62411C>A		intron_variant	Intron 2 of 4		XP_011512528.1
RCAN2	XM_024446301.2	c.225+62411C>A		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+62411C>A		intron_variant	Intron 2 of 4	1	NM_001251974.2	ENSP00000360425.1
RCAN2	ENST00000306764.11	c.225+62411C>A		intron_variant	Intron 2 of 4	1		ENSP00000305223.7

Frequencies

GnomAD3 genomes AF: 0.408 AC: 62033 AN: 151936 Hom.: 15611 Cov.: 33

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.545

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.391

Gnomad EAS AF: 0.594

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.627

Gnomad MID AF: 0.335

Gnomad NFE AF: 0.533

Gnomad OTH AF: 0.420

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

GnomAD4 genome AF: 0.408 AC: 62051 AN: 152054 Hom.: 15621 Cov.: 33 AF XY: 0.414 AC XY: 30763 AN XY: 74326

African (AFR) AF: 0.100 AC: 4149 AN: 41508

American (AMR) AF: 0.463 AC: 7061 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.391 AC: 1355 AN: 3464

East Asian (EAS) AF: 0.594 AC: 3079 AN: 5180

South Asian (SAS) AF: 0.435 AC: 2091 AN: 4810

European-Finnish (FIN) AF: 0.627 AC: 6632 AN: 10570

Middle Eastern (MID) AF: 0.333 AC: 98 AN: 294

European-Non Finnish (NFE) AF: 0.533 AC: 36194 AN: 67946

Other (OTH) AF: 0.424 AC: 895 AN: 2110

Alfa AF: 0.471 Hom.: 2323

Bravo AF: 0.383

Asia WGS AF: 0.494 AC: 1715 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.98
DANN	Benign	0.70
PhyloP100		-0.50
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: rs953887; hg19: chr6-46362078;