2-47161627-A-AGGG

Position:

• chr2-47161627-A-AGGG

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001743.6(CALM2):​c.421+95_421+96insCCC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.216 in 152,090 control chromosomes in the GnomAD database, including 5,709 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.22 (5709 hom., cov: 31)
• Consequence: CALM2 NM_001743.6 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0380

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 -10 ACMG points.

• BP6: Variant 2-47161627-A-AGGG is Benign according to our data. Variant chr2-47161627-A-AGGG is described in ClinVar as [Benign]. Clinvar id is 1290819.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	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CALM2	NM_001743.6	c.421+95_421+96insCCC		intron_variant		ENST00000272298.12	NP_001734.1
CALM2	NM_001305624.1	c.565+95_565+96insCCC		intron_variant			NP_001292553.1
CALM2	NM_001305625.2	c.313+95_313+96insCCC		intron_variant			NP_001292554.1
CALM2	NM_001305626.1	c.313+95_313+96insCCC		intron_variant			NP_001292555.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CALM2	ENST00000272298.12	c.421+95_421+96insCCC		intron_variant		1	NM_001743.6	ENSP00000272298	P1

Frequencies

GnomAD3 genomes AF: 0.216 AC: 32810 AN: 151970 Hom.: 5691 Cov.: 31

Gnomad AFR AF: 0.479

Gnomad AMI AF: 0.143

Gnomad AMR AF: 0.198

Gnomad ASJ AF: 0.0621

Gnomad EAS AF: 0.0623

Gnomad SAS AF: 0.218

Gnomad FIN AF: 0.101

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0992

Gnomad OTH AF: 0.189

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

GnomAD4 genome AF: 0.216 AC: 32879 AN: 152090 Hom.: 5709 Cov.: 31 AF XY: 0.214 AC XY: 15886 AN XY: 74356

Gnomad4 AFR AF: 0.479

Gnomad4 AMR AF: 0.198

Gnomad4 ASJ AF: 0.0621

Gnomad4 EAS AF: 0.0624

Gnomad4 SAS AF: 0.217

Gnomad4 FIN AF: 0.101

Gnomad4 NFE AF: 0.0992

Gnomad4 OTH AF: 0.187

Alfa AF: 0.777 Hom.: 30

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jan 06, 2019

- -

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs1289216990; hg19: chr2-47388766;