2-47161626-C-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -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

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.765

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

long QT syndrome
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
long QT syndrome 15
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae)
catecholaminergic polymorphic ventricular tachycardia
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Genomics England PanelApp, ClinGen, G2P

CALM2 links:

ENSG00000273269 (HGNC:):

ENSG00000273269 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001743.6. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM2	NM_001743.6	MANE Select	c.421+97G>C	intron	N/A	NP_001734.1	P0DP24
CALM2	NM_001305624.1		c.565+97G>C	intron	N/A	NP_001292553.1	P0DP24
CALM2	NM_001305625.2		c.313+97G>C	intron	N/A	NP_001292554.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CALM2	ENST00000272298.12	TSL:1 MANE Select	c.421+97G>C	intron	N/A	ENSP00000272298.7	P0DP24
ENSG00000273269	ENST00000422269.1	TSL:2	n.101-8610G>C	intron	N/A	ENSP00000476793.1	V9GYI7
CALM2	ENST00000460218.5	TSL:1	n.3861+97G>C	intron	N/A

Frequencies

GnomAD3 genomes

AF:

0.766

AC:

101575

AN:

132530

Hom.:

36364

Cov.:

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

African (AFR)

AF:

0.617

AC:

8169

AN:

13240

American (AMR)

AF:

0.751

AC:

16578

AN:

22074

Ashkenazi Jewish (ASJ)

AF:

0.872

AC:

14955

AN:

17156

East Asian (EAS)

AF:

0.867

AC:

29447

AN:

33976

South Asian (SAS)

AF:

0.787

AC:

40869

AN:

51936

European-Finnish (FIN)

AF:

0.821

AC:

38425

AN:

46824

Middle Eastern (MID)

AF:

0.854

AC:

2466

AN:

2888

European-Non Finnish (NFE)

AF:

0.808

AC:

549068

AN:

679938

Other (OTH)

AF:

0.799

AC:

31719

AN:

39720

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

7892

15784

23676

31568

39460

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11384

22768

34152

45536

56920

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.766

AC:

101619

AN:

132586

Hom.:

36381

Cov.:

AF XY:

0.770

AC XY:

50065

AN XY:

65042

show subpopulations

African (AFR)

AF:

0.612

AC:

16486

AN:

26942

American (AMR)

AF:

0.768

AC:

10733

AN:

13984

Ashkenazi Jewish (ASJ)

AF:

0.881

AC:

3011

AN:

3416

East Asian (EAS)

AF:

0.869

AC:

4431

AN:

5100

South Asian (SAS)

AF:

0.774

AC:

3398

AN:

4392

European-Finnish (FIN)

AF:

0.826

AC:

8432

AN:

10212

Middle Eastern (MID)

AF:

0.830

AC:

239

AN:

288

European-Non Finnish (NFE)

AF:

0.806

AC:

52749

AN:

65446

Other (OTH)

AF:

0.764

AC:

1481

AN:

1938

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

1482

2964

4446

5928

7410

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

792

1584

2376

3168

3960

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.838

Hom.:

1308

Bravo

AF:

0.883

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Long QT syndrome 15 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.021

(source)

DANN

Benign

0.36

PhyloP100

-0.77

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over