Variant chr1-237801833-A-ATTTT details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1BS2

The NM_001035.3(RYR2):c.14091-14_14091-11dupTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000013 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00017 ( 0 hom. )

Consequence

RYR2
NM_001035.3 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.362

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:

RYR2 (HGNC:):

RYR2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BS1

Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.000172 (209/1217940) while in subpopulation SAS AF= 0.00185 (135/72792). AF 95% confidence interval is 0.0016. There are 0 homozygotes in gnomad4_exome. There are 140 alleles in male gnomad4_exome subpopulation. Median coverage is 12. This position pass quality control queck.

BS2

High AC in GnomAdExome4 at 209 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
RYR2	NM_001035.3 linkuse as main transcript	c.14091-14_14091-11dupTTTT		intron_variant		ENST00000366574.7	NP_001026.2	Q92736-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7 linkuse as main transcript	c.14091-14_14091-11dupTTTT		intron_variant		1	NM_001035.3	ENSP00000355533.2		Q92736-1
RYR2	ENST00000609119.2 linkuse as main transcript	n.5183-14_5183-11dupTTTT		intron_variant		5		ENSP00000499659.2		A0A590UK06

Frequencies

GnomAD3 genomes

AF:

0.0000135

AC:

AN:

148158

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000422

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.000172

AC:

209

AN:

1217940

Hom.:

Cov.:

AF XY:

0.000230

AC XY:

140

AN XY:

608220

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000515

Gnomad4 ASJ exome

AF:

0.0000441

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00185

Gnomad4 FIN exome

AF:

0.0000736

Gnomad4 NFE exome

AF:

0.0000629

Gnomad4 OTH exome

AF:

0.000156

GnomAD4 genome

AF:

0.0000135

AC:

AN:

148158

Hom.:

Cov.:

AF XY:

0.0000277

AC XY:

AN XY:

72088

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000422

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over