1-237801833-ATTTTT-ATTTTTTTTTT

Variant names:

• chr1-237801833-A-ATTTTT
• NM_001035.3:c.14091-15_14091-11dupTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001035.3(RYR2):​c.14091-15_14091-11dupTTTTT 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: not found (cov: 0)
  • Exomes 𝑓: 0.000011 (0 hom.)
• Consequence: RYR2 NM_001035.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.362

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 -8 ACMG points.

• BS1: Variant frequency is greater than expected in population sas. gnomad4_exome allele frequency = 0.0000115 (14/1218054) while in subpopulation SAS AF= 0.000124 (9/72834). AF 95% confidence interval is 0.000064. There are 0 homozygotes in gnomad4_exome. There are 8 alleles in male gnomad4_exome subpopulation. Median coverage is 12. This position pass quality control queck.
• BS2: High AC in GnomAdExome4 at 14 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
RYR2	NM_001035.3	c.14091-15_14091-11dupTTTTT		intron_variant	Intron 97 of 104	ENST00000366574.7	NP_001026.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
RYR2	ENST00000366574.7	c.14091-23_14091-22insTTTTT		intron_variant	Intron 97 of 104	1	NM_001035.3	ENSP00000355533.2
RYR2	ENST00000609119.2	n.*5183-23_*5183-22insTTTTT		intron_variant	Intron 96 of 103	5		ENSP00000499659.2

Frequencies

GnomAD3 genomes Cov.: 0

GnomAD4 exome AF: 0.0000115 AC: 14 AN: 1218054 Hom.: 0 Cov.: 12 AF XY: 0.0000132 AC XY: 8 AN XY: 608290

Gnomad4 AFR exome AF: 0.0000356

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.000124

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000434

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr1-237965133;