chr2-47174925-G-C

Position:

• chr2-47174925-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The ENST00000272298.12(CALM2):​c.3+1516C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.889 in 151,998 control chromosomes in the GnomAD database, including 60,045 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 0.89 (60045 hom., cov: 28)
• Consequence: CALM2 ENST00000272298.12 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.101

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.67).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM2	NM_001743.6	c.3+1516C>G		intron_variant		ENST00000272298.12	NP_001734.1
CALM2	NM_001305624.1	c.101+1516C>G		intron_variant			NP_001292553.1
CALM2	NM_001305625.2	c.-106+1924C>G		intron_variant			NP_001292554.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM2	ENST00000272298.12	c.3+1516C>G		intron_variant		1	NM_001743.6	ENSP00000272298	P1

Frequencies

GnomAD3 genomes AF: 0.888 AC: 134943 AN: 151880 Hom.: 59983 Cov.: 28

Gnomad AFR AF: 0.888

Gnomad AMI AF: 0.875

Gnomad AMR AF: 0.902

Gnomad ASJ AF: 0.933

Gnomad EAS AF: 0.918

Gnomad SAS AF: 0.923

Gnomad FIN AF: 0.901

Gnomad MID AF: 0.921

Gnomad NFE AF: 0.876

Gnomad OTH AF: 0.894

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

GnomAD4 genome AF: 0.889 AC: 135064 AN: 151998 Hom.: 60045 Cov.: 28 AF XY: 0.891 AC XY: 66218 AN XY: 74302

Gnomad4 AFR AF: 0.888

Gnomad4 AMR AF: 0.902

Gnomad4 ASJ AF: 0.933

Gnomad4 EAS AF: 0.918

Gnomad4 SAS AF: 0.923

Gnomad4 FIN AF: 0.901

Gnomad4 NFE AF: 0.877

Gnomad4 OTH AF: 0.895

Alfa AF: 0.888 Hom.: 7450

Bravo AF: 0.887

Asia WGS AF: 0.923 AC: 3207 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	10
DANN	Benign	0.69

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: rs1693869; hg19: chr2-47402064;