rs2241695

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBA1

The NM_015981.4(CAMK2A):c.1238-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,476,122 control chromosomes in the GnomAD database, including 222,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

Frequency

Genomes: 𝑓 0.47 ( 18552 hom., cov: 31)

Exomes 𝑓: 0.55 ( 204353 hom. )

Consequence

CAMK2A
NM_015981.4 intron

Scores

Clinical Significance

Benign criteria provided, single submitter B:2

Conservation

PhyloP100: -0.527

Publications

24 publications found

Variant links:

Genes affected

CAMK2A (HGNC:1460): (calcium/calmodulin dependent protein kinase II alpha) The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This calcium calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2018]

CAMK2A Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen
intellectual disability, autosomal dominant 53
Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
autosomal dominant non-syndromic intellectual disability
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
intellectual disability, autosomal recessive 63
Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

CAMK2A links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_015981.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.74).

BP6

Variant 5-150223261-C-T is Benign according to our data. Variant chr5-150223261-C-T is described in ClinVar as Benign. ClinVar VariationId is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAMK2A	NM_015981.4	MANE Select	c.1238-44G>A	intron	N/A	NP_057065.2
CAMK2A	NM_001363989.1		c.1238-44G>A	intron	N/A	NP_001350918.1	Q9UQM7-2
CAMK2A	NM_001363990.1		c.1205-44G>A	intron	N/A	NP_001350919.1	Q7LDD5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CAMK2A	ENST00000671881.1	MANE Select	c.1238-44G>A	intron	N/A	ENSP00000500386.1	Q9UQM7-2
CAMK2A	ENST00000348628.11	TSL:1	c.1205-44G>A	intron	N/A	ENSP00000261793.8	Q9UQM7-1
CAMK2A	ENST00000398376.8	TSL:1	c.1034-44G>A	intron	N/A	ENSP00000381412.4	A0A5K1VW76

Frequencies

GnomAD3 genomes

AF:

0.469

AC:

71264

AN:

151810

Hom.:

18547

Cov.:

show subpopulations

Gnomad AFR

AF:

0.223

Gnomad AMI

AF:

0.610

Gnomad AMR

AF:

0.517

Gnomad ASJ

AF:

0.608

Gnomad EAS

AF:

0.626

Gnomad SAS

AF:

0.495

Gnomad FIN

AF:

0.614

Gnomad MID

AF:

0.557

Gnomad NFE

AF:

0.562

Gnomad OTH

AF:

0.501

GnomAD2 exomes

AF:

0.537

AC:

117021

AN:

217732

AF XY:

0.543

show subpopulations

Gnomad AFR exome

AF:

0.225

Gnomad AMR exome

AF:

0.483

Gnomad ASJ exome

AF:

0.624

Gnomad EAS exome

AF:

0.617

Gnomad FIN exome

AF:

0.628

Gnomad NFE exome

AF:

0.572

Gnomad OTH exome

AF:

0.563

GnomAD4 exome

AF:

0.551

AC:

729794

AN:

1324194

Hom.:

204353

Cov.:

AF XY:

0.551

AC XY:

365227

AN XY:

662766

show subpopulations

African (AFR)

AF:

0.213

AC:

6641

AN:

31126

American (AMR)

AF:

0.482

AC:

20355

AN:

42244

Ashkenazi Jewish (ASJ)

AF:

0.616

AC:

15351

AN:

24930

East Asian (EAS)

AF:

0.646

AC:

24952

AN:

38606

South Asian (SAS)

AF:

0.492

AC:

40518

AN:

82324

European-Finnish (FIN)

AF:

0.617

AC:

28682

AN:

46502

Middle Eastern (MID)

AF:

0.529

AC:

2846

AN:

5384

European-Non Finnish (NFE)

AF:

0.562

AC:

559950

AN:

997198

Other (OTH)

AF:

0.546

AC:

30499

AN:

55880

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

16628

33255

49883

66510

83138

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

14952

29904

44856

59808

74760

<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:

0.469

AC:

71282

AN:

151928

Hom.:

18552

Cov.:

AF XY:

0.474

AC XY:

35232

AN XY:

74254

show subpopulations

African (AFR)

AF:

0.223

AC:

9235

AN:

41474

American (AMR)

AF:

0.517

AC:

7881

AN:

15252

Ashkenazi Jewish (ASJ)

AF:

0.608

AC:

2109

AN:

3468

East Asian (EAS)

AF:

0.626

AC:

3216

AN:

5140

South Asian (SAS)

AF:

0.496

AC:

2385

AN:

4804

European-Finnish (FIN)

AF:

0.614

AC:

6492

AN:

10572

Middle Eastern (MID)

AF:

0.582

AC:

171

AN:

294

European-Non Finnish (NFE)

AF:

0.562

AC:

38178

AN:

67904

Other (OTH)

AF:

0.502

AC:

1059

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1753

3506

5258

7011

8764

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

638

1276

1914

2552

3190

<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:

0.543

Hom.:

42071

Bravo

AF:

0.452

Asia WGS

AF:

0.537

AC:

1867

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Intellectual disability, autosomal dominant 53 (1)

Intellectual disability, autosomal recessive 63 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.74

CADD

Benign

5.8

(source)

DANN

Benign

0.72

PhyloP100

-0.53

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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