1-237801833-ATTTTT-ATTTT

Variant names:

• chr1-237801833-AT-A
• rs35563566
• NM_001035.3:c.14091-11delT

Variant summary

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

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

• Frequency:
  • Genomes: 𝑓 0.0018 (0 hom., cov: 0)
  • Exomes 𝑓: 0.099 (1 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• 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 -16 ACMG points.

• BP6: Variant 1-237801833-AT-A is Benign according to our data. Variant chr1-237801833-AT-A is described in ClinVar as [Likely_benign]. Clinvar id is 43737.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237801833-AT-A is described in Lovd as [Benign]. Variant chr1-237801833-AT-A is described in Lovd as [Likely_benign].
• BA1: GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.142 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.14091-11delT		intron_variant	Intron 97 of 104	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.14091-22delT		intron_variant	Intron 97 of 104	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.*5183-22delT		intron_variant	Intron 96 of 103	5		ENSP00000499659.2

Frequencies

GnomAD3 genomes AF: 0.00177 AC: 261 AN: 147836 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00253

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00122

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000786

Gnomad SAS AF: 0.000634

Gnomad FIN AF: 0.00568

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00109

Gnomad OTH AF: 0.00347

GnomAD4 exome AF: 0.0993 AC: 111640 AN: 1124718 Hom.: 1 Cov.: 12 AF XY: 0.0998 AC XY: 56002 AN XY: 561062

Gnomad4 AFR exome AF: 0.106

Gnomad4 AMR exome AF: 0.145

Gnomad4 ASJ exome AF: 0.0904

Gnomad4 EAS exome AF: 0.0545

Gnomad4 SAS exome AF: 0.0974

Gnomad4 FIN exome AF: 0.110

Gnomad4 NFE exome AF: 0.0992

Gnomad4 OTH exome AF: 0.0967

GnomAD4 genome AF: 0.00179 AC: 265 AN: 147904 Hom.: 0 Cov.: 0 AF XY: 0.00188 AC XY: 135 AN XY: 71976

Gnomad4 AFR AF: 0.00260

Gnomad4 AMR AF: 0.00122

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000789

Gnomad4 SAS AF: 0.000635

Gnomad4 FIN AF: 0.00568

Gnomad4 NFE AF: 0.00109

Gnomad4 OTH AF: 0.00393

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Sep 16, 2011

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

14091-11delT in intron 97 of RYR2: This variant is not expected to have clinical significance because it is located outside the conserved +/- 1, 2 region of the splicing consensus sequence and as part of a polyT stretch. This variant has b een reported in dbSNP (rs72027983 & rs55683196) without frequency information. -

not provided Benign:1

Aug 30, 2019

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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;