Variant chr2-47161625-TCA-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_001743.6(CALM2):c.421+96_421+97del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 1,104,254 control chromosomes in the GnomAD database, including 14,446 homozygotes. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.22 ( 5697 hom., cov: 29)

Exomes 𝑓: 0.11 ( 8749 hom. )

Consequence

CALM2
NM_001743.6 intron

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.765

Variant links:

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 2-47161625-TCA-T is Benign according to our data. Variant chr2-47161625-TCA-T is described in ClinVar as [Benign]. Clinvar id is 674617.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein
CALM2	NM_001743.6 linkuse as main transcript	c.421+96_421+97del	intron_variant	ENST00000272298.12	NP_001734.1
CALM2	NM_001305624.1 linkuse as main transcript	c.565+96_565+97del	intron_variant		NP_001292553.1
CALM2	NM_001305625.2 linkuse as main transcript	c.313+96_313+97del	intron_variant		NP_001292554.1
CALM2	NM_001305626.1 linkuse as main transcript	c.313+96_313+97del	intron_variant		NP_001292555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM2	ENST00000272298.12 linkuse as main transcript	c.421+96_421+97del		intron_variant		1	NM_001743.6	ENSP00000272298	P1

Frequencies

GnomAD3 genomes

AF:

0.216

AC:

32787

AN:

151680

Hom.:

5679

Cov.:

show subpopulations

Gnomad AFR

AF:

0.480

Gnomad AMI

AF:

0.143

Gnomad AMR

AF:

0.199

Gnomad ASJ

AF:

0.0621

Gnomad EAS

AF:

0.0625

Gnomad SAS

AF:

0.219

Gnomad FIN

AF:

0.101

Gnomad MID

AF:

0.123

Gnomad NFE

AF:

0.0993

Gnomad OTH

AF:

0.189

GnomAD4 exome

AF:

0.109

AC:

103556

AN:

952454

Hom.:

8749

AF XY:

0.110

AC XY:

52790

AN XY:

481958

show subpopulations

Gnomad4 AFR exome

AF:

0.483

Gnomad4 AMR exome

AF:

0.223

Gnomad4 ASJ exome

AF:

0.0608

Gnomad4 EAS exome

AF:

0.0642

Gnomad4 SAS exome

AF:

0.194

Gnomad4 FIN exome

AF:

0.104

Gnomad4 NFE exome

AF:

0.0896

Gnomad4 OTH exome

AF:

0.122

GnomAD4 genome

AF:

0.216

AC:

32856

AN:

151800

Hom.:

5697

Cov.:

AF XY:

0.214

AC XY:

15879

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.480

Gnomad4 AMR

AF:

0.199

Gnomad4 ASJ

AF:

0.0621

Gnomad4 EAS

AF:

0.0626

Gnomad4 SAS

AF:

0.218

Gnomad4 FIN

AF:

0.101

Gnomad4 NFE

AF:

0.0993

Gnomad4 OTH

AF:

0.187

Alfa

AF:

0.126

Hom.:

Asia WGS

AF:

0.166

AC:

578

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over