1-237589774-ATT-ATTT

Variant names:

• chr1-237589774-A-AT
• rs11331089
• NM_001035.3:c.3599-9dupT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_001035.3(RYR2):​c.3599-9dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00028 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00032 (0 hom.)
• Consequence: RYR2 NM_001035.3 splice_region, intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.467

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 -10 ACMG points.

• BP6: Variant 1-237589774-A-AT is Benign according to our data. Variant chr1-237589774-A-AT is described in ClinVar as [Benign]. Clinvar id is 1534662.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000285 (43/151042) while in subpopulation AFR AF= 0.000901 (37/41056). AF 95% confidence interval is 0.000672. There are 0 homozygotes in gnomad4. There are 24 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 43 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.3599-9dupT		splice_region_variant, intron_variant	Intron 29 of 104	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.3599-19_3599-18insT		intron_variant	Intron 29 of 104	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.3599-19_3599-18insT		intron_variant	Intron 29 of 103	5		ENSP00000499659.2
RYR2	ENST00000660292.2	c.3599-19_3599-18insT		intron_variant	Intron 29 of 105			ENSP00000499787.2
RYR2	ENST00000659194.3	c.3599-19_3599-18insT		intron_variant	Intron 29 of 104			ENSP00000499653.3

Frequencies

GnomAD3 genomes AF: 0.000285 AC: 43 AN: 150932 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000904

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000660

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000628

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000295

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000321 AC: 456 AN: 1422388 Hom.: 0 Cov.: 0 AF XY: 0.000338 AC XY: 239 AN XY: 707976

Gnomad4 AFR exome AF: 0.00131

Gnomad4 AMR exome AF: 0.000230

Gnomad4 ASJ exome AF: 0.000196

Gnomad4 EAS exome AF: 0.000232

Gnomad4 SAS exome AF: 0.00102

Gnomad4 FIN exome AF: 0.0000190

Gnomad4 NFE exome AF: 0.000268

Gnomad4 OTH exome AF: 0.000238

GnomAD4 genome AF: 0.000285 AC: 43 AN: 151042 Hom.: 0 Cov.: 0 AF XY: 0.000325 AC XY: 24 AN XY: 73742

Gnomad4 AFR AF: 0.000901

Gnomad4 AMR AF: 0.0000660

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000628

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000295

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Catecholaminergic polymorphic ventricular tachycardia 1 Benign:1

Jan 02, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs11331089; hg19: chr1-237753074;