rs3797617

chr5-150239936-G-Achr5-150239936-G-C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015981.4(CAMK2A):c.985-200C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.134 in 151,944 control chromosomes in the GnomAD database, including 1,563 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1563 hom., cov: 32)
• Consequence: CAMK2A NM_015981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.391

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.209 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2A	NM_015981.4	c.985-200C>T		intron_variant		ENST00000671881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2A	ENST00000671881.1	c.985-200C>T		intron_variant			NM_015981.4	P3

Frequencies

GnomAD3 genomes AF: 0.134 AC: 20325 AN: 151826 Hom.: 1565 Cov.: 32

Gnomad AFR AF: 0.0583

Gnomad AMI AF: 0.0890

Gnomad AMR AF: 0.215

Gnomad ASJ AF: 0.149

Gnomad EAS AF: 0.113

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.150

Gnomad MID AF: 0.187

Gnomad NFE AF: 0.161

Gnomad OTH AF: 0.158

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.134 AC: 20325 AN: 151944 Hom.: 1563 Cov.: 32 AF XY: 0.136 AC XY: 10064 AN XY: 74254

Gnomad4 AFR AF: 0.0583

Gnomad4 AMR AF: 0.215

Gnomad4 ASJ AF: 0.149

Gnomad4 EAS AF: 0.113

Gnomad4 SAS AF: 0.116

Gnomad4 FIN AF: 0.150

Gnomad4 NFE AF: 0.161

Gnomad4 OTH AF: 0.155

Alfa AF: 0.134 Hom.: 699

Bravo AF: 0.138

Asia WGS AF: 0.100 AC: 347 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	0.29
Dann	Benign	0.77

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: rs3797617; hg19: chr5-149619499;