rs35563566

Positions:

• chr1-237801833-ATT-A
• chr1-237801833-ATT-AT
• chr1-237801833-ATT-ATTT
• chr1-237801833-ATT-ATTTT
• chr1-237801833-ATT-ATTTTT
• chr1-237801833-ATT-ATTTTTT
• chr1-237801833-ATT-ATTTTTTTTTT
• chr1-237801833-ATT-ATTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BS1 BS2

The NM_001035.3(RYR2):​c.14091-12_14091-11del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00116 in 1,354,864 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in Lovd as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0000067 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0013 (0 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

Genes affected

RYR2 (HGNC:10484): (ryanodine receptor 2) This gene encodes a ryanodine receptor found in cardiac muscle sarcoplasmic reticulum. The encoded protein is one of the components of a calcium channel, composed of a tetramer of the ryanodine receptor proteins and a tetramer of FK506 binding protein 1B proteins, that supplies calcium to cardiac muscle. Mutations in this gene are associated with stress-induced polymorphic ventricular tachycardia and arrhythmogenic right ventricular dysplasia. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -9 ACMG points.

• BP6: Variant 1-237801833-ATT-A is Benign according to our data. Variant chr1-237801833-ATT-A is described in Lovd as [Benign].
• BS1: Variant frequency is greater than expected in population amr. gnomad4_exome allele frequency = 0.00131 (1575/1206654) while in subpopulation AMR AF= 0.00222 (85/38332). AF 95% confidence interval is 0.00184. There are 0 homozygotes in gnomad4_exome. There are 832 alleles in male gnomad4_exome subpopulation. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 1575 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.14091-12_14091-11del		intron_variant		ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.14091-12_14091-11del		intron_variant		1	NM_001035.3	P1

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148140 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000149

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00131 AC: 1575 AN: 1206654 Hom.: 0 AF XY: 0.00138 AC XY: 832 AN XY: 602628

Gnomad4 AFR exome AF: 0.00115

Gnomad4 AMR exome AF: 0.00222

Gnomad4 ASJ exome AF: 0.00124

Gnomad4 EAS exome AF: 0.000305

Gnomad4 SAS exome AF: 0.00209

Gnomad4 FIN exome AF: 0.00114

Gnomad4 NFE exome AF: 0.00127

Gnomad4 OTH exome AF: 0.00116

GnomAD4 genome AF: 0.00000675 AC: 1 AN: 148210 Hom.: 0 Cov.: 0 AF XY: 0.0000139 AC XY: 1 AN XY: 72162

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000149

Gnomad4 OTH AF: 0.00

Alfa AF: 0.00393 Hom.: 457

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs35563566; hg19: chr1-237965133;