rs775247848
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Variant summary
Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP6_Very_StrongBS2
The NM_001743.6(CALM2):c.422-9_422-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000748 in 1,484,440 control chromosomes in the GnomAD database, with no homozygous occurrence. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00014 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000068 ( 0 hom. )
Consequence
CALM2
NM_001743.6 splice_region, splice_polypyrimidine_tract, intron
NM_001743.6 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 1.99
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 -12 ACMG points.
BP6
?
Variant 2-47160810-AAAG-A is Benign according to our data. Variant chr2-47160810-AAAG-A is described in ClinVar as [Likely_benign]. Clinvar id is 415527.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CALM2 | NM_001743.6 | c.422-9_422-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000272298.12 | |||
CALM2 | NM_001305624.1 | c.566-9_566-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
CALM2 | NM_001305625.2 | c.314-9_314-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ||||
CALM2 | NM_001305626.1 | c.314-9_314-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CALM2 | ENST00000272298.12 | c.422-9_422-7del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001743.6 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000139 AC: 21AN: 151190Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.0000442 AC: 7AN: 158268Hom.: 0 AF XY: 0.0000118 AC XY: 1AN XY: 85034
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GnomAD4 exome AF: 0.0000675 AC: 90AN: 1333250Hom.: 0 AF XY: 0.0000650 AC XY: 43AN XY: 661874
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GnomAD4 genome ? AF: 0.000139 AC: 21AN: 151190Hom.: 0 Cov.: 0 AF XY: 0.000122 AC XY: 9AN XY: 73758
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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 | Jan 31, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | May 19, 2022 | See Variant Classification Assertion Criteria. - |
Computational scores
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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