1-237801833-ATT-ATTTT

Position:

• chr1-237801833-ATT-ATTTT

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001035.3(RYR2):​c.14091-12_14091-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.047 (206 hom., cov: 0)
  • Exomes 𝑓: 0.031 (149 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:5
• 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 -16 ACMG points.

• BP6: Variant 1-237801833-A-ATT is Benign according to our data. Variant chr1-237801833-A-ATT is described in ClinVar as [Benign]. Clinvar id is 1174686.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0876 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.14091-12_14091-11dupTT		intron_variant		ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.14091-12_14091-11dupTT		intron_variant		1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.*5183-12_*5183-11dupTT		intron_variant		5		ENSP00000499659.2

Frequencies

GnomAD3 genomes AF: 0.0470 AC: 6960 AN: 148108 Hom.: 206 Cov.: 0

Gnomad AFR AF: 0.0903

Gnomad AMI AF: 0.0122

Gnomad AMR AF: 0.0325

Gnomad ASJ AF: 0.0289

Gnomad EAS AF: 0.0356

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0190

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.0305

Gnomad OTH AF: 0.0524

GnomAD4 exome AF: 0.0314 AC: 37946 AN: 1209318 Hom.: 149 Cov.: 12 AF XY: 0.0317 AC XY: 19146 AN XY: 603888

Gnomad4 AFR exome AF: 0.0788

Gnomad4 AMR exome AF: 0.0212

Gnomad4 ASJ exome AF: 0.0316

Gnomad4 EAS exome AF: 0.0254

Gnomad4 SAS exome AF: 0.0458

Gnomad4 FIN exome AF: 0.0179

Gnomad4 NFE exome AF: 0.0296

Gnomad4 OTH exome AF: 0.0355

GnomAD4 genome AF: 0.0470 AC: 6959 AN: 148180 Hom.: 206 Cov.: 0 AF XY: 0.0462 AC XY: 3335 AN XY: 72148

Gnomad4 AFR AF: 0.0901

Gnomad4 AMR AF: 0.0324

Gnomad4 ASJ AF: 0.0289

Gnomad4 EAS AF: 0.0357

Gnomad4 SAS AF: 0.0406

Gnomad4 FIN AF: 0.0190

Gnomad4 NFE AF: 0.0305

Gnomad4 OTH AF: 0.0519

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:3

Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, criteria provided, single submitter	clinical testing	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	Nov 28, 2022	- -

Cardiomyopathy Benign:1

Benign, criteria provided, single submitter

clinical testing

CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario

Dec 10, 2020

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 19, 2019

- -

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;