1-237801833-A-ATTT

Position:

• chr1-237801833-A-ATTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001035.3(RYR2):​c.14091-13_14091-11dupTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0060 (19 hom., cov: 0)
  • Exomes 𝑓: 0.0054 (33 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]

RYR2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0711 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.14091-13_14091-11dupTTT		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.14091-13_14091-11dupTTT		intron_variant		1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.*5183-13_*5183-11dupTTT		intron_variant		5		ENSP00000499659.2

Frequencies

GnomAD3 genomes AF: 0.00601 AC: 890 AN: 148148 Hom.: 18 Cov.: 0

Gnomad AFR AF: 0.000769

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00560

Gnomad ASJ AF: 0.00409

Gnomad EAS AF: 0.000590

Gnomad SAS AF: 0.0771

Gnomad FIN AF: 0.00500

Gnomad MID AF: 0.0256

Gnomad NFE AF: 0.00483

Gnomad OTH AF: 0.00743

GnomAD4 exome AF: 0.00537 AC: 6528 AN: 1216664 Hom.: 33 Cov.: 12 AF XY: 0.00651 AC XY: 3953 AN XY: 607552

Gnomad4 AFR exome AF: 0.00157

Gnomad4 AMR exome AF: 0.00191

Gnomad4 ASJ exome AF: 0.00318

Gnomad4 EAS exome AF: 0.000304

Gnomad4 SAS exome AF: 0.0445

Gnomad4 FIN exome AF: 0.00415

Gnomad4 NFE exome AF: 0.00271

Gnomad4 OTH exome AF: 0.00631

GnomAD4 genome AF: 0.00602 AC: 892 AN: 148218 Hom.: 19 Cov.: 0 AF XY: 0.00711 AC XY: 513 AN XY: 72164

Gnomad4 AFR AF: 0.000767

Gnomad4 AMR AF: 0.00559

Gnomad4 ASJ AF: 0.00409

Gnomad4 EAS AF: 0.000592

Gnomad4 SAS AF: 0.0777

Gnomad4 FIN AF: 0.00500

Gnomad4 NFE AF: 0.00483

Gnomad4 OTH AF: 0.00735

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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;