chr6-46321984-T-A

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001251974.2(RCAN2):​c.226-73088A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001251974.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCAN2	NM_001251974.2	MANE Select	c.226-73088A>T		intron	N/A	NP_001238903.1
	RCAN2	NM_001251973.2		c.226-73088A>T		intron	N/A	NP_001238902.1
	RCAN2	NM_005822.4		c.87+3409A>T		intron	N/A	NP_005813.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	RCAN2	ENST00000371374.6	TSL:1 MANE Select	c.226-73088A>T		intron	N/A	ENSP00000360425.1
	RCAN2	ENST00000306764.11	TSL:1	c.226-73088A>T		intron	N/A	ENSP00000305223.7
	RCAN2	ENST00000330430.10	TSL:1	c.87+3409A>T		intron	N/A	ENSP00000329454.6

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 10

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	6.2
DANN	Benign	0.41
PhyloP100		0.86

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;