1-237042458-G-GGCC

Position:

• chr1-237042458-G-GGCC

Variant summary

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

The NM_001035.3(RYR2):​c.-50_-48dupCCG variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00026 in 1,228,100 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0012 (0 hom., cov: 33)
  • Exomes 𝑓: 0.00013 (0 hom.)
• Consequence: RYR2 NM_001035.3 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.215

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 -10 ACMG points.

• BP6: Variant 1-237042458-G-GGCC is Benign according to our data. Variant chr1-237042458-G-GGCC is described in ClinVar as [Benign]. Clinvar id is 201174.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00116 (176/151914) while in subpopulation AFR AF= 0.00354 (147/41536). AF 95% confidence interval is 0.00307. There are 0 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 176 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3	c.-50_-48dupCCG		5_prime_UTR_variant	1/105	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574	c.-50_-48dupCCG		5_prime_UTR_variant	1/105	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.-50_-48dupCCG		non_coding_transcript_exon_variant	1/104	5		ENSP00000499659.2
RYR2	ENST00000609119.2	n.-50_-48dupCCG		5_prime_UTR_variant	1/104	5		ENSP00000499659.2

Frequencies

GnomAD3 genomes AF: 0.00116 AC: 176 AN: 151806 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.00353

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00125

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000620

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000884

Gnomad OTH AF: 0.000960

GnomAD4 exome AF: 0.000133 AC: 143 AN: 1076186 Hom.: 0 Cov.: 25 AF XY: 0.000157 AC XY: 80 AN XY: 508380

Gnomad4 AFR exome AF: 0.00300

Gnomad4 AMR exome AF: 0.000497

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000388

Gnomad4 SAS exome AF: 0.0000518

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000585

Gnomad4 OTH exome AF: 0.000351

GnomAD4 genome AF: 0.00116 AC: 176 AN: 151914 Hom.: 0 Cov.: 33 AF XY: 0.00120 AC XY: 89 AN XY: 74266

Gnomad4 AFR AF: 0.00354

Gnomad4 AMR AF: 0.00124

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000414

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000884

Gnomad4 OTH AF: 0.000950

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 25, 2014

The variant is found in CARDIOMYOPATHY panel(s). -

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: rs794728699; hg19: chr1-237205758;