NM_001251974.2:c.571+10856T>A

Variant names:

• chr6-46235892-A-T
• rs2584076
• NM_001251974.2:c.571+10856T>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.571+10856T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.747 in 152,046 control chromosomes in the GnomAD database, including 44,328 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 0.75 (44328 hom., cov: 32)
• Consequence: RCAN2 NM_001251974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.01
• 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]

ENSG00000307590 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.871 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.571+10856T>A		intron_variant	Intron 4 of 4	ENST00000371374.6	NP_001238903.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RCAN2	ENST00000371374.6	c.571+10856T>A		intron_variant	Intron 4 of 4	1	NM_001251974.2	ENSP00000360425.1

Frequencies

GnomAD3 genomes AF: 0.747 AC: 113471 AN: 151928 Hom.: 44315 Cov.: 32

Gnomad AFR AF: 0.527

Gnomad AMI AF: 0.886

Gnomad AMR AF: 0.624

Gnomad ASJ AF: 0.858

Gnomad EAS AF: 0.715

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.904

Gnomad MID AF: 0.803

Gnomad NFE AF: 0.877

Gnomad OTH AF: 0.744

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

GnomAD4 genome AF: 0.747 AC: 113521 AN: 152046 Hom.: 44328 Cov.: 32 AF XY: 0.745 AC XY: 55400 AN XY: 74324

African (AFR) AF: 0.527 AC: 21817 AN: 41416

American (AMR) AF: 0.623 AC: 9514 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.858 AC: 2978 AN: 3472

East Asian (EAS) AF: 0.715 AC: 3696 AN: 5168

South Asian (SAS) AF: 0.766 AC: 3689 AN: 4818

European-Finnish (FIN) AF: 0.904 AC: 9582 AN: 10594

Middle Eastern (MID) AF: 0.805 AC: 235 AN: 292

European-Non Finnish (NFE) AF: 0.877 AC: 59632 AN: 67992

Other (OTH) AF: 0.744 AC: 1570 AN: 2110

Alfa AF: 0.811 Hom.: 6380

Bravo AF: 0.714

Asia WGS AF: 0.707 AC: 2461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	0.050
DANN	Benign	0.66
PhyloP100		-2.0
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs2584076; hg19: chr6-46203629;