5-150222566-C-G

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_015981.4(CAMK2A):​c.*144G>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00113 in 910,248 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0042 ( 1 hom., cov: 32)
Exomes 𝑓: 0.00052 ( 3 hom. )

Consequence

CAMK2A
NM_015981.4 3_prime_UTR

Scores

2

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.739

Publications

0 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]
SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

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=-0.78).
BP6
Variant 5-150222566-C-G is Benign according to our data. Variant chr5-150222566-C-G is described in CliVar as Likely_benign. Clinvar id is 2655915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150222566-C-G is described in CliVar as Likely_benign. Clinvar id is 2655915.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150222566-C-G is described in CliVar as Likely_benign. Clinvar id is 2655915.Status of the report is criteria_provided_single_submitter, 1 stars.
BS1
Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00419 (637/152072) while in subpopulation AFR AF = 0.0147 (608/41486). AF 95% confidence interval is 0.0137. There are 1 homozygotes in GnomAd4. There are 284 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
BS2
High Homozygotes in GnomAdExome4 at 3 AD,AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CAMK2ANM_015981.4 linkc.*144G>C 3_prime_UTR_variant Exon 19 of 19 ENST00000671881.1 NP_057065.2 A8K161Q8IWE0

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CAMK2AENST00000671881.1 linkc.*144G>C 3_prime_UTR_variant Exon 19 of 19 NM_015981.4 ENSP00000500386.1 Q9UQM7-2

Frequencies

GnomAD3 genomes
AF:
0.00417
AC:
633
AN:
151954
Hom.:
1
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.0146
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000983
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00316
Gnomad NFE
AF:
0.0000736
Gnomad OTH
AF:
0.00383
GnomAD2 exomes
AF:
0.000930
AC:
160
AN:
172132
AF XY:
0.000692
show subpopulations
Gnomad AFR exome
AF:
0.0133
Gnomad AMR exome
AF:
0.000844
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000682
Gnomad OTH exome
AF:
0.000848
GnomAD4 exome
AF:
0.000517
AC:
392
AN:
758176
Hom.:
3
Cov.:
10
AF XY:
0.000408
AC XY:
163
AN XY:
399218
show subpopulations
African (AFR)
AF:
0.0147
AC:
292
AN:
19834
American (AMR)
AF:
0.000748
AC:
27
AN:
36120
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
21238
East Asian (EAS)
AF:
0.00
AC:
0
AN:
34564
South Asian (SAS)
AF:
0.0000147
AC:
1
AN:
68010
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
43622
Middle Eastern (MID)
AF:
0.00157
AC:
7
AN:
4454
European-Non Finnish (NFE)
AF:
0.0000406
AC:
20
AN:
492950
Other (OTH)
AF:
0.00120
AC:
45
AN:
37384
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.495
Heterozygous variant carriers
0
28
57
85
114
142
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Exome Hom
Variant carriers
0
10
20
30
40
50
<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:
0.00419
AC:
637
AN:
152072
Hom.:
1
Cov.:
32
AF XY:
0.00382
AC XY:
284
AN XY:
74318
show subpopulations
African (AFR)
AF:
0.0147
AC:
608
AN:
41486
American (AMR)
AF:
0.000981
AC:
15
AN:
15286
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3472
East Asian (EAS)
AF:
0.00
AC:
0
AN:
5144
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4804
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10600
Middle Eastern (MID)
AF:
0.00340
AC:
1
AN:
294
European-Non Finnish (NFE)
AF:
0.0000736
AC:
5
AN:
67964
Other (OTH)
AF:
0.00379
AC:
8
AN:
2112
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.501
Heterozygous variant carriers
0
33
67
100
134
167
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Variant carriers
0
10
20
30
40
50
<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:
0.00201
Hom.:
0
Bravo
AF:
0.00474
Asia WGS
AF:
0.000577
AC:
2
AN:
3478

ClinVar

Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Benign:1
Jan 01, 2024
CeGaT Center for Human Genetics Tuebingen
Significance:Likely benign
Review Status:criteria provided, single submitter
Collection Method:clinical testing

CAMK2A: PP2, BS1 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.78
CADD
Benign
12
DANN
Benign
0.63
PhyloP100
0.74
Mutation Taster
=100/0
polymorphism

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

Other links and lift over

dbSNP: rs151118217; hg19: chr5-149602129; API