1-115700223-ATTT-AT

Variant names:

• chr1-115700223-ATT-A
• rs11347859
• NM_001232.4:c.*1016_*1017delAA

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001232.4(CASQ2):​c.*1016_*1017delAA variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0015 in 148,428 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0015 (0 hom., cov: 0)
  • Exomes 𝑓: 0.0052 (0 hom.)
• Consequence: CASQ2 NM_001232.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.400

Genes affected

CASQ2 (HGNC:1513): (calsequestrin 2) The protein encoded by this gene specifies the cardiac muscle family member of the calsequestrin family. Calsequestrin is localized to the sarcoplasmic reticulum in cardiac and slow skeletal muscle cells. The protein is a calcium binding protein that stores calcium for muscle function. Mutations in this gene cause stress-induced polymorphic ventricular tachycardia, also referred to as catecholaminergic polymorphic ventricular tachycardia 2 (CPVT2), a disease characterized by bidirectional ventricular tachycardia that may lead to cardiac arrest. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00149 (220/148040) while in subpopulation AFR AF= 0.00425 (172/40448). AF 95% confidence interval is 0.00373. There are 0 homozygotes in gnomad4. There are 115 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CASQ2	NM_001232.4	c.*1016_*1017delAA		3_prime_UTR_variant	Exon 11 of 11	ENST00000261448.6	NP_001223.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CASQ2	ENST00000261448	c.*1016_*1017delAA		3_prime_UTR_variant	Exon 11 of 11	1	NM_001232.4	ENSP00000261448.5
CASQ2	ENST00000488931.2	n.*1588_*1589delAA		non_coding_transcript_exon_variant	Exon 13 of 13	3		ENSP00000518226.1
CASQ2	ENST00000488931.2	n.*1588_*1589delAA		3_prime_UTR_variant	Exon 13 of 13	3		ENSP00000518226.1

Frequencies

GnomAD3 genomes AF: 0.00149 AC: 221 AN: 147958 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.00426

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000602

Gnomad ASJ AF: 0.000292

Gnomad EAS AF: 0.000198

Gnomad SAS AF: 0.00297

Gnomad FIN AF: 0.000417

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000285

Gnomad OTH AF: 0.000489

GnomAD4 exome AF: 0.00515 AC: 2 AN: 388 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 234

Gnomad4 FIN exome AF: 0.00524

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.00149 AC: 220 AN: 148040 Hom.: 0 Cov.: 0 AF XY: 0.00160 AC XY: 115 AN XY: 72092

Gnomad4 AFR AF: 0.00425

Gnomad4 AMR AF: 0.000535

Gnomad4 ASJ AF: 0.000292

Gnomad4 EAS AF: 0.000198

Gnomad4 SAS AF: 0.00298

Gnomad4 FIN AF: 0.000417

Gnomad4 NFE AF: 0.000285

Gnomad4 OTH AF: 0.000486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Other links and lift over

dbSNP: rs11347859; hg19: chr1-116242844;