Variant chr1-237742271-T-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.11092-25T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0018 ( 0 hom., cov: 26)

Exomes 𝑓: 0.28 ( 32 hom. )

Failed GnomAD Quality Control

Consequence

RYR2
NM_001035.3 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.0580

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.88).

BP6

Variant 1-237742271-T-C is Benign according to our data. Variant chr1-237742271-T-C is described in ClinVar as [Benign]. Clinvar id is 257197.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-237742271-T-C is described in Lovd as [Benign].

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.331 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.11092-25T>C		intron_variant		ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	Effect	TSL	MANE	Protein	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.11092-25T>C	intron_variant	1	NM_001035.3	ENSP00000355533.2	Q92736-1
RYR2	ENST00000661330.1 linkuse as main transcript	c.898-25T>C	intron_variant			ENSP00000499393.2	A0A590UJF6
RYR2	ENST00000609119.2 linkuse as main transcript	n.*2127-25T>C	intron_variant	5		ENSP00000499659.2	A0A590UK06

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

158

AN:

88202

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00154

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000451

Gnomad ASJ

AF:

0.00192

Gnomad EAS

AF:

0.000288

Gnomad SAS

AF:

0.000822

Gnomad FIN

AF:

0.00495

Gnomad MID

AF:

0.00505

Gnomad NFE

AF:

0.00209

Gnomad OTH

AF:

0.000816

GnomAD3 exomes

AF:

0.0884

AC:

6209

AN:

70234

Hom.:

AF XY:

0.0898

AC XY:

3416

AN XY:

38022

show subpopulations

Gnomad AFR exome

AF:

0.0148

Gnomad AMR exome

AF:

0.101

Gnomad ASJ exome

AF:

0.0827

Gnomad EAS exome

AF:

0.0697

Gnomad SAS exome

AF:

0.0923

Gnomad FIN exome

AF:

0.0866

Gnomad NFE exome

AF:

0.0971

Gnomad OTH exome

AF:

0.0998

GnomAD4 exome

AF:

0.282

AC:

64636

AN:

229308

Hom.:

Cov.:

AF XY:

0.282

AC XY:

31956

AN XY:

113430

show subpopulations

Gnomad4 AFR exome

AF:

0.112

Gnomad4 AMR exome

AF:

0.347

Gnomad4 ASJ exome

AF:

0.325

Gnomad4 EAS exome

AF:

0.327

Gnomad4 SAS exome

AF:

0.283

Gnomad4 FIN exome

AF:

0.282

Gnomad4 NFE exome

AF:

0.281

Gnomad4 OTH exome

AF:

0.288

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00179

AC:

158

AN:

88210

Hom.:

Cov.:

AF XY:

0.00206

AC XY:

AN XY:

43294

show subpopulations

Gnomad4 AFR

AF:

0.00154

Gnomad4 AMR

AF:

0.000451

Gnomad4 ASJ

AF:

0.00192

Gnomad4 EAS

AF:

0.000288

Gnomad4 SAS

AF:

0.000829

Gnomad4 FIN

AF:

0.00495

Gnomad4 NFE

AF:

0.00209

Gnomad4 OTH

AF:

0.000809

Alfa

AF:

0.0674

Hom.:

179

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	clinical testing	GeneDx	Aug 19, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

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

-0.88

CADD

Benign

1.7

DANN

Benign

0.38

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