1-237042322-C-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001035.3(RYR2):c.-200C>A variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0245 in 301,022 control chromosomes in the GnomAD database, including 515 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.043 (470 hom., cov: 33)
  • Exomes 𝑓: 0.0056 (45 hom.)
• Consequence: RYR2 NM_001035.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.127

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.77).
• BP6: Variant 1-237042322-C-A is Benign according to our data. Variant chr1-237042322-C-A is described in ClinVar as [Benign]. Clinvar id is 1224907.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.144 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
RYR2	NM_001035.3	c.-200C>A		5_prime_UTR_variant	1/105	ENST00000366574.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
RYR2	ENST00000366574.7	c.-200C>A		5_prime_UTR_variant	1/105	1	NM_001035.3	P1
RYR2	ENST00000659194.3	c.-200C>A		5_prime_UTR_variant	1/105
RYR2	ENST00000660292.2	c.-200C>A		5_prime_UTR_variant	1/106
RYR2	ENST00000609119.2	c.-200C>A		5_prime_UTR_variant, NMD_transcript_variant	1/104	5

Frequencies

GnomAD3 genomes AF: 0.0431 AC: 6529 AN: 151400 Hom.: 470 Cov.: 33

Gnomad AFR AF: 0.147

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0185

Gnomad ASJ AF: 0.000289

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0127

Gnomad NFE AF: 0.00112

Gnomad OTH AF: 0.0336

GnomAD4 exome AF: 0.00560 AC: 838 AN: 149514 Hom.: 45 Cov.: 4 AF XY: 0.00488 AC XY: 374 AN XY: 76632

Gnomad4 AFR exome AF: 0.159

Gnomad4 AMR exome AF: 0.0153

Gnomad4 ASJ exome AF: 0.000804

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000889

Gnomad4 OTH exome AF: 0.0183

GnomAD4 genome AF: 0.0432 AC: 6544 AN: 151508 Hom.: 470 Cov.: 33 AF XY: 0.0422 AC XY: 3129 AN XY: 74064

Gnomad4 AFR AF: 0.147

Gnomad4 AMR AF: 0.0185

Gnomad4 ASJ AF: 0.000289

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00112

Gnomad4 OTH AF: 0.0332

Alfa AF: 0.00191 Hom.: 3

Bravo AF: 0.0492

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK:

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 26, 2018

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.77

Cadd

Benign

16

Dann

Benign

0.78

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: rs138019171; hg19: chr1-237205622;