chr6-46321984-T-C

Variant names:

• chr6-46321984-T-C
• rs1442219
• NM_001251974.2:c.226-73088A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001251974.2(RCAN2):​c.226-73088A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0135 in 152,298 control chromosomes in the GnomAD database, including 55 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 0.014 (55 hom., cov: 33)
• Consequence: RCAN2 NM_001251974.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.858
• 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]

ENSG00000307576 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0135 (2057/152298) while in subpopulation AFR AF = 0.045 (1870/41556). AF 95% confidence interval is 0.0433. There are 55 homozygotes in GnomAd4. There are 976 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 55 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RCAN2	NM_001251974.2	c.226-73088A>G		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.226-73088A>G		intron_variant	Intron 2 of 4	1	NM_001251974.2	ENSP00000360425.1

Frequencies

GnomAD3 genomes AF: 0.0135 AC: 2050 AN: 152180 Hom.: 55 Cov.: 33

Gnomad AFR AF: 0.0450

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00929

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000265

Gnomad OTH AF: 0.0115

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

GnomAD4 genome AF: 0.0135 AC: 2057 AN: 152298 Hom.: 55 Cov.: 33 AF XY: 0.0131 AC XY: 976 AN XY: 74482

African (AFR) AF: 0.0450 AC: 1870 AN: 41556

American (AMR) AF: 0.00928 AC: 142 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5178

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4824

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10622

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000265 AC: 18 AN: 68030

Other (OTH) AF: 0.0114 AC: 24 AN: 2110

Alfa AF: 0.0132 Hom.: 10

Bravo AF: 0.0159

Asia WGS AF: 0.00173 AC: 6 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	6.5
DANN	Benign	0.53
PhyloP100		0.86
Mutation Taster		=100/0	polymorphism

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: rs1442219; hg19: chr6-46289721;