rs815802

Variant names:

• chr2-47164910-G-A
• rs815802
• NM_001743.6:c.35-2248C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-47164910-G-A
• chr2-47164910-G-C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001743.6(CALM2):​c.35-2248C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.898 in 152,192 control chromosomes in the GnomAD database, including 61,413 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.90 (61413 hom., cov: 31)
• Consequence: CALM2 NM_001743.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.790
• Publications: 4 publications found

Genes affected

CALM2 (HGNC:1445): (calmodulin 2) This gene is a member of the calmodulin gene family. There are three distinct calmodulin genes dispersed throughout the genome that encode the identical protein, but differ at the nucleotide level. Calmodulin is a calcium binding protein that plays a role in signaling pathways, cell cycle progression and proliferation. Several infants with severe forms of long-QT syndrome (LQTS) who displayed life-threatening ventricular arrhythmias together with delayed neurodevelopment and epilepsy were found to have mutations in either this gene or another member of the calmodulin gene family (PMID:23388215). Mutations in this gene have also been identified in patients with less severe forms of LQTS (PMID:24917665), while mutations in another calmodulin gene family member have been associated with catecholaminergic polymorphic ventricular tachycardia (CPVT)(PMID:23040497), a rare disorder thought to be the cause of a significant fraction of sudden cardiac deaths in young individuals. Pseudogenes of this gene are found on chromosomes 10, 13, and 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Mar 2015]

CALM2 Gene-Disease associations (from GenCC):

• long QT syndrome

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
• long QT syndrome 15

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
• catecholaminergic polymorphic ventricular tachycardia

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, ClinGen, G2P

ENSG00000273269 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.914 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001743.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM2	NM_001743.6	MANE Select	c.35-2248C>T		intron	N/A	NP_001734.1	P0DP24
	CALM2	NM_001305624.1		c.179-2248C>T		intron	N/A	NP_001292553.1	P0DP24
	CALM2	NM_001305625.2		c.-74-2248C>T		intron	N/A	NP_001292554.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CALM2	ENST00000272298.12	TSL:1 MANE Select	c.35-2248C>T		intron	N/A	ENSP00000272298.7	P0DP24
	ENSG00000273269	ENST00000422269.1	TSL:2	n.100+5824C>T		intron	N/A	ENSP00000476793.1	V9GYI7
	CALM2	ENST00000460218.5	TSL:1	n.3475-2248C>T		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.898 AC: 136515 AN: 152074 Hom.: 61354 Cov.: 31

Gnomad AFR AF: 0.896

Gnomad AMI AF: 0.893

Gnomad AMR AF: 0.923

Gnomad ASJ AF: 0.943

Gnomad EAS AF: 0.875

Gnomad SAS AF: 0.935

Gnomad FIN AF: 0.862

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.895

Gnomad OTH AF: 0.909

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.898 AC: 136633 AN: 152192 Hom.: 61413 Cov.: 31 AF XY: 0.898 AC XY: 66822 AN XY: 74402

African (AFR) AF: 0.896 AC: 37168 AN: 41498

American (AMR) AF: 0.923 AC: 14115 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.943 AC: 3275 AN: 3472

East Asian (EAS) AF: 0.875 AC: 4530 AN: 5176

South Asian (SAS) AF: 0.936 AC: 4513 AN: 4820

European-Finnish (FIN) AF: 0.862 AC: 9131 AN: 10596

Middle Eastern (MID) AF: 0.946 AC: 278 AN: 294

European-Non Finnish (NFE) AF: 0.895 AC: 60891 AN: 68014

Other (OTH) AF: 0.909 AC: 1919 AN: 2112

Alfa AF: 0.898 Hom.: 123102

Bravo AF: 0.900

Asia WGS AF: 0.907 AC: 3154 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	6.8
DANN	Benign	0.87
PhyloP100		0.79
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs815802; hg19: chr2-47392049;