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2-47161626-C-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001743.6(CALM2):c.421+97G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 1,040,338 control chromosomes in the GnomAD database, including 321,512 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.77 ( 36381 hom., cov: 29)
Exomes 𝑓: 0.81 ( 285131 hom. )

Consequence

CALM2
NM_001743.6 intron

Scores

2

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

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]

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-1.03).
BP6
Variant 2-47161626-C-G is Benign according to our data. Variant chr2-47161626-C-G is described in ClinVar as [Benign]. Clinvar id is 674616.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.847 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
CALM2NM_001743.6 linkuse as main transcriptc.421+97G>C intron_variant ENST00000272298.12
CALM2NM_001305624.1 linkuse as main transcriptc.565+97G>C intron_variant
CALM2NM_001305625.2 linkuse as main transcriptc.313+97G>C intron_variant
CALM2NM_001305626.1 linkuse as main transcriptc.313+97G>C intron_variant

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
CALM2ENST00000272298.12 linkuse as main transcriptc.421+97G>C intron_variant 1 NM_001743.6 P1

Frequencies

GnomAD3 genomes
AF:
0.766
AC:
101575
AN:
132530
Hom.:
36364
Cov.:
29
show subpopulations
Gnomad AFR
AF:
0.612
Gnomad AMI
AF:
0.759
Gnomad AMR
AF:
0.768
Gnomad ASJ
AF:
0.881
Gnomad EAS
AF:
0.869
Gnomad SAS
AF:
0.773
Gnomad FIN
AF:
0.826
Gnomad MID
AF:
0.815
Gnomad NFE
AF:
0.806
Gnomad OTH
AF:
0.763
GnomAD4 exome
AF:
0.806
AC:
731696
AN:
907752
Hom.:
285131
AF XY:
0.807
AC XY:
370573
AN XY:
459464
show subpopulations
Gnomad4 AFR exome
AF:
0.617
Gnomad4 AMR exome
AF:
0.751
Gnomad4 ASJ exome
AF:
0.872
Gnomad4 EAS exome
AF:
0.867
Gnomad4 SAS exome
AF:
0.787
Gnomad4 FIN exome
AF:
0.821
Gnomad4 NFE exome
AF:
0.808
Gnomad4 OTH exome
AF:
0.799
GnomAD4 genome
AF:
0.766
AC:
101619
AN:
132586
Hom.:
36381
Cov.:
29
AF XY:
0.770
AC XY:
50065
AN XY:
65042
show subpopulations
Gnomad4 AFR
AF:
0.612
Gnomad4 AMR
AF:
0.768
Gnomad4 ASJ
AF:
0.881
Gnomad4 EAS
AF:
0.869
Gnomad4 SAS
AF:
0.774
Gnomad4 FIN
AF:
0.826
Gnomad4 NFE
AF:
0.806
Gnomad4 OTH
AF:
0.764
Alfa
AF:
0.838
Hom.:
1308
Bravo
AF:
0.883

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

Long QT syndrome 15 Benign:1
Benign, criteria provided, single submitterclinical testingGenome-Nilou LabJul 14, 2021- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingGeneDxJun 14, 2018This 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
BayesDel_noAF
Benign
-1.0
Cadd
Benign
0.021
Dann
Benign
0.36

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.

Other links and lift over

dbSNP: rs2454084; hg19: chr2-47388765; API