7-44220122-G-A
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_001220.5(CAMK2B):c.1941C>T(p.Asp647=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000962 in 1,611,430 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00018 ( 0 hom., cov: 34)
Exomes 𝑓: 0.000088 ( 2 hom. )
Consequence
CAMK2B
NM_001220.5 synonymous
NM_001220.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.86
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 -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.78).
BP6
?
Variant 7-44220122-G-A is Benign according to our data. Variant chr7-44220122-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1528196.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-1.86 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000177 (27/152372) while in subpopulation AFR AF= 0.000289 (12/41592). AF 95% confidence interval is 0.000166. There are 0 homozygotes in gnomad4. There are 14 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
BS2
?
High AC in GnomAd at 27 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CAMK2B | NM_001220.5 | c.1941C>T | p.Asp647= | synonymous_variant | 23/24 | ENST00000395749.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CAMK2B | ENST00000395749.7 | c.1941C>T | p.Asp647= | synonymous_variant | 23/24 | 1 | NM_001220.5 |
Frequencies
GnomAD3 genomes ? AF: 0.000177 AC: 27AN: 152254Hom.: 0 Cov.: 34
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GnomAD3 exomes AF: 0.0000939 AC: 23AN: 244838Hom.: 0 AF XY: 0.0000826 AC XY: 11AN XY: 133246
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GnomAD4 exome AF: 0.0000877 AC: 128AN: 1459058Hom.: 2 Cov.: 55 AF XY: 0.0000964 AC XY: 70AN XY: 725850
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
CAMK2B-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 28, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 18, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at