Variant 1-237659956-A-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001035.3(RYR2):c.8209-29A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0504 in 1,484,206 control chromosomes in the GnomAD database, including 2,139 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). There are indicators that this mutation may affect the branch point..

Frequency

Genomes: 𝑓 0.060 ( 331 hom., cov: 32)

Exomes 𝑓: 0.049 ( 1808 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 0.925

Variant links:

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

This place is a probable branch point but likely benign (scored 3 / 10). Computational evidence support a benign effect (BayesDel_noAF=-0.69).

BP6

Variant 1-237659956-A-C is Benign according to our data. Variant chr1-237659956-A-C is described in ClinVar as [Benign]. Clinvar id is 257218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0883 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3 link	c.8209-29A>C		intron_variant		ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RYR2	ENST00000366574.7 link	c.8209-29A>C	intron_variant	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000609119.2 link	n.8209-29A>C	intron_variant	5		ENSP00000499659.2	A0A590UK06
RYR2	ENST00000660292.2 link	c.8209-29A>C	intron_variant			ENSP00000499787.2	A0A590UKB7
RYR2	ENST00000659194.3 link	c.8209-29A>C	intron_variant			ENSP00000499653.3	A0A590UJZ8

Frequencies

GnomAD3 genomes

AF:

0.0597

AC:

9082

AN:

152128

Hom.:

329

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0907

Gnomad AMI

AF:

0.0252

Gnomad AMR

AF:

0.0482

Gnomad ASJ

AF:

0.0767

Gnomad EAS

AF:

0.000193

Gnomad SAS

AF:

0.00703

Gnomad FIN

AF:

0.0535

Gnomad MID

AF:

0.0633

Gnomad NFE

AF:

0.0522

Gnomad OTH

AF:

0.0598

GnomAD3 exomes

AF:

0.0452

AC:

8864

AN:

196322

Hom.:

246

AF XY:

0.0444

AC XY:

4754

AN XY:

107012

show subpopulations

Gnomad AFR exome

AF:

0.0884

Gnomad AMR exome

AF:

0.0308

Gnomad ASJ exome

AF:

0.0739

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00665

Gnomad FIN exome

AF:

0.0582

Gnomad NFE exome

AF:

0.0535

Gnomad OTH exome

AF:

0.0466

GnomAD4 exome

AF:

0.0493

AC:

65686

AN:

1331962

Hom.:

1808

Cov.:

AF XY:

0.0481

AC XY:

32016

AN XY:

665620

show subpopulations

Gnomad4 AFR exome

AF:

0.0971

Gnomad4 AMR exome

AF:

0.0330

Gnomad4 ASJ exome

AF:

0.0715

Gnomad4 EAS exome

AF:

0.0000268

Gnomad4 SAS exome

AF:

0.00684

Gnomad4 FIN exome

AF:

0.0573

Gnomad4 NFE exome

AF:

0.0526

Gnomad4 OTH exome

AF:

0.0488

GnomAD4 genome

AF:

0.0597

AC:

9096

AN:

152244

Hom.:

331

Cov.:

AF XY:

0.0584

AC XY:

4348

AN XY:

74444

show subpopulations

Gnomad4 AFR

AF:

0.0907

Gnomad4 AMR

AF:

0.0481

Gnomad4 ASJ

AF:

0.0767

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00704

Gnomad4 FIN

AF:

0.0535

Gnomad4 NFE

AF:

0.0522

Gnomad4 OTH

AF:

0.0591

Alfa

AF:

0.0559

Hom.:

Bravo

AF:

0.0605

Asia WGS

AF:

0.00983

AC:

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 18, 2018	This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.69

CADD

Benign

7.5

DANN

Benign

0.72

BranchPoint Hunter

3.0

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over