rs1193912501
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Variant summary
Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2
The NM_001743.6(CALM2):c.421+10T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000996 in 1,606,496 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 31)
Exomes 𝑓: 0.0000069 ( 0 hom. )
Consequence
CALM2
NM_001743.6 intron
NM_001743.6 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.669
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 -16 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.86).
BP6
?
Variant 2-47161713-A-C is Benign according to our data. Variant chr2-47161713-A-C is described in ClinVar as [Likely_benign]. Clinvar id is 458194.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALM2 | NM_001743.6 | c.421+10T>G | intron_variant | ENST00000272298.12 | |||
CALM2 | NM_001305624.1 | c.565+10T>G | intron_variant | ||||
CALM2 | NM_001305625.2 | c.313+10T>G | intron_variant | ||||
CALM2 | NM_001305626.1 | c.313+10T>G | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALM2 | ENST00000272298.12 | c.421+10T>G | intron_variant | 1 | NM_001743.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152198Hom.: 0 Cov.: 31
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GnomAD3 exomes AF: 0.0000163 AC: 4AN: 245188Hom.: 0 AF XY: 0.0000151 AC XY: 2AN XY: 132656
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GnomAD4 exome AF: 0.00000688 AC: 10AN: 1454298Hom.: 0 Cov.: 30 AF XY: 0.00000691 AC XY: 5AN XY: 723432
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GnomAD4 genome ? AF: 0.0000394 AC: 6AN: 152198Hom.: 0 Cov.: 31 AF XY: 0.0000269 AC XY: 2AN XY: 74370
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Long QT syndrome 1 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Aug 30, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 02, 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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at