7-44220069-A-G
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_ModerateBP6_Very_StrongBS2
The NM_001220.5(CAMK2B):c.1994T>C(p.Leu665Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000265 in 1,587,652 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.000039 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000025 ( 0 hom. )
Consequence
CAMK2B
NM_001220.5 missense
NM_001220.5 missense
Scores
2
10
4
Clinical Significance
Conservation
PhyloP100: 2.88
Genes affected
CAMK2B (HGNC:1461): (calcium/calmodulin dependent protein kinase II beta) The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a beta chain. It is possible that distinct isoforms of this chain have different cellular localizations and interact differently with calmodulin. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2014]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, CAMK2B
BP4
?
Computational evidence support a benign effect (MetaRNN=0.1543884).
BP6
?
Variant 7-44220069-A-G is Benign according to our data. Variant chr7-44220069-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1644161.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS2
?
High AC in GnomAd at 6 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAMK2B | NM_001220.5 | c.1994T>C | p.Leu665Pro | missense_variant | 23/24 | ENST00000395749.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMK2B | ENST00000395749.7 | c.1994T>C | p.Leu665Pro | missense_variant | 23/24 | 1 | NM_001220.5 |
Frequencies
GnomAD3 genomes ? AF: 0.0000394 AC: 6AN: 152184Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000522 AC: 11AN: 210702Hom.: 0 AF XY: 0.0000261 AC XY: 3AN XY: 115106
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GnomAD4 exome AF: 0.0000251 AC: 36AN: 1435468Hom.: 0 Cov.: 31 AF XY: 0.0000238 AC XY: 17AN XY: 712928
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 02, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 22, 2022 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Benign
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
T
MutationTaster
Benign
D;D;D;D;D;D;D;D;D;D;D
PrimateAI
Uncertain
T
PROVEAN
Uncertain
D;D;D;D;D;D;D;D;N;D;D
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D;D;D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;D;D;D;D;D;D;D
Polyphen
D;D;D;.;D;D;P;D;D;D;D
Vest4
MutPred
0.26
.;.;Gain of disorder (P = 0.0059);.;.;.;.;.;.;.;.;
MVP
MPC
2.3
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
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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