1-237742270-CTTTTT-CTTTTTTT

Variant names:

• chr1-237742270-C-CTT
• rs397516499
• NM_001035.3:c.11092-12_11092-11dupTT

Variant summary

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

The NM_001035.3(RYR2):​c.11092-12_11092-11dupTT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00436 in 1,178,502 control chromosomes in the GnomAD database, including 29 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.011 (29 hom., cov: 26)
  • Exomes 𝑓: 0.0035 (0 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0580

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 1-237742270-C-CTT is Benign according to our data. Variant chr1-237742270-C-CTT is described in ClinVar as [Likely_benign]. Clinvar id is 1191841.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0106 (1467/138538) while in subpopulation AFR AF= 0.038 (1389/36518). AF 95% confidence interval is 0.0364. There are 29 homozygotes in gnomad4. There are 687 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1467 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.11092-12_11092-11dupTT		intron_variant	Intron 79 of 104	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.11092-26_11092-25insTT		intron_variant	Intron 79 of 104	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000661330.1	c.898-26_898-25insTT		intron_variant	Intron 10 of 11			ENSP00000499393.2
RYR2	ENST00000609119.2	n.*2127-26_*2127-25insTT		intron_variant	Intron 77 of 103	5		ENSP00000499659.2

Frequencies

GnomAD3 genomes AF: 0.0105 AC: 1461 AN: 138530 Hom.: 28 Cov.: 26

Gnomad AFR AF: 0.0379

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00388

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000226

Gnomad FIN AF: 0.000248

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000109

Gnomad OTH AF: 0.00738

GnomAD4 exome AF: 0.00353 AC: 3670 AN: 1039964 Hom.: 0 Cov.: 0 AF XY: 0.00334 AC XY: 1732 AN XY: 519072

Gnomad4 AFR exome AF: 0.0325

Gnomad4 AMR exome AF: 0.00393

Gnomad4 ASJ exome AF: 0.00136

Gnomad4 EAS exome AF: 0.00149

Gnomad4 SAS exome AF: 0.00404

Gnomad4 FIN exome AF: 0.000910

Gnomad4 NFE exome AF: 0.00286

Gnomad4 OTH exome AF: 0.00415

GnomAD4 genome AF: 0.0106 AC: 1467 AN: 138538 Hom.: 29 Cov.: 26 AF XY: 0.0102 AC XY: 687 AN XY: 67134

Gnomad4 AFR AF: 0.0380

Gnomad4 AMR AF: 0.00388

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000227

Gnomad4 FIN AF: 0.000248

Gnomad4 NFE AF: 0.000109

Gnomad4 OTH AF: 0.00734

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Aug 07, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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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: rs397516499; hg19: chr1-237905570;