5-150223045-A-G

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_015981.4(CAMK2A):c.1410T>C(p.Asp470=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,614,194 control chromosomes in the GnomAD database, including 680,740 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.94 (66995 hom., cov: 36)
  • Exomes 𝑓: 0.92 (613745 hom.)
• Consequence: CAMK2A NM_015981.4 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.439

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]

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.54).
• BP6: Variant 5-150223045-A-G is Benign according to our data. Variant chr5-150223045-A-G is described in ClinVar as [Benign]. Clinvar id is 1192689.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-0.439 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.977 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2A	NM_015981.4	c.1410T>C	p.Asp470=	synonymous_variant	18/19	ENST00000671881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2A	ENST00000671881.1	c.1410T>C	p.Asp470=	synonymous_variant	18/19		NM_015981.4	P3

Frequencies

GnomAD3 genomes AF: 0.937 AC: 142647 AN: 152226 Hom.: 66935 Cov.: 36

Gnomad AFR AF: 0.985

Gnomad AMI AF: 0.861

Gnomad AMR AF: 0.954

Gnomad ASJ AF: 0.917

Gnomad EAS AF: 0.834

Gnomad SAS AF: 0.836

Gnomad FIN AF: 0.935

Gnomad MID AF: 0.946

Gnomad NFE AF: 0.921

Gnomad OTH AF: 0.950

GnomAD3 exomes AF: 0.918 AC: 228671 AN: 249086 Hom.: 105244 AF XY: 0.912 AC XY: 123271 AN XY: 135110

Gnomad AFR exome AF: 0.987

Gnomad AMR exome AF: 0.967

Gnomad ASJ exome AF: 0.914

Gnomad EAS exome AF: 0.831

Gnomad SAS exome AF: 0.845

Gnomad FIN exome AF: 0.931

Gnomad NFE exome AF: 0.925

Gnomad OTH exome AF: 0.916

GnomAD4 exome AF: 0.916 AC: 1338932 AN: 1461850 Hom.: 613745 Cov.: 74 AF XY: 0.914 AC XY: 664456 AN XY: 727224

Gnomad4 AFR exome AF: 0.987

Gnomad4 AMR exome AF: 0.967

Gnomad4 ASJ exome AF: 0.917

Gnomad4 EAS exome AF: 0.848

Gnomad4 SAS exome AF: 0.849

Gnomad4 FIN exome AF: 0.931

Gnomad4 NFE exome AF: 0.919

Gnomad4 OTH exome AF: 0.914

GnomAD4 genome AF: 0.937 AC: 142767 AN: 152344 Hom.: 66995 Cov.: 36 AF XY: 0.936 AC XY: 69713 AN XY: 74490

Gnomad4 AFR AF: 0.985

Gnomad4 AMR AF: 0.954

Gnomad4 ASJ AF: 0.917

Gnomad4 EAS AF: 0.834

Gnomad4 SAS AF: 0.836

Gnomad4 FIN AF: 0.935

Gnomad4 NFE AF: 0.921

Gnomad4 OTH AF: 0.948

Alfa AF: 0.927 Hom.: 102184

Bravo AF: 0.942

Asia WGS AF: 0.834 AC: 2901 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual disability, autosomal recessive 63 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

Intellectual disability, autosomal dominant 53 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 27, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.54
Cadd	Benign	0.10
Dann	Benign	0.59

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

LitVar

Other links and lift over

dbSNP: rs2241694; hg19: chr5-149602608; COSMIC: COSV62245600; COSMIC: COSV62245600;