Variant 5-150223045-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.439

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 links:

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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=-0.54).

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	Protein	UniProt
CAMK2A	NM_015981.4 linkuse as main transcript	c.1410T>C	p.Asp470=	synonymous_variant	18/19	ENST00000671881.1	NP_057065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2A	ENST00000671881.1 linkuse as main transcript	c.1410T>C	p.Asp470=	synonymous_variant	18/19		NM_015981.4	ENSP00000500386	P3	Q9UQM7-2

Frequencies

GnomAD3 genomes

AF:

0.937

AC:

142647

AN:

152226

Hom.:

66935

Cov.:

show subpopulations

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

show subpopulations

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.:

AF XY:

0.914

AC XY:

664456

AN XY:

727224

show subpopulations

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.:

AF XY:

0.936

AC XY:

69713

AN XY:

74490

show subpopulations

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

LINK: link

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over