5-150229830-G-A

Position:

• chr5-150229830-G-A

Variant summary

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

The NM_015981.4(CAMK2A):​c.1142+1475C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.31 in 152,146 control chromosomes in the GnomAD database, including 7,675 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 0.31 (7675 hom., cov: 32)
• Consequence: CAMK2A NM_015981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0120

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.364 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2A	NM_015981.4	c.1142+1475C>T		intron_variant		ENST00000671881.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2A	ENST00000671881.1	c.1142+1475C>T		intron_variant			NM_015981.4	P3

Frequencies

GnomAD3 genomes AF: 0.310 AC: 47081 AN: 152028 Hom.: 7673 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.251

Gnomad AMR AF: 0.372

Gnomad ASJ AF: 0.292

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.335

Gnomad FIN AF: 0.320

Gnomad MID AF: 0.363

Gnomad NFE AF: 0.361

Gnomad OTH AF: 0.322

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

GnomAD4 genome AF: 0.310 AC: 47098 AN: 152146 Hom.: 7675 Cov.: 32 AF XY: 0.309 AC XY: 22981 AN XY: 74366

Gnomad4 AFR AF: 0.217

Gnomad4 AMR AF: 0.372

Gnomad4 ASJ AF: 0.292

Gnomad4 EAS AF: 0.168

Gnomad4 SAS AF: 0.334

Gnomad4 FIN AF: 0.320

Gnomad4 NFE AF: 0.361

Gnomad4 OTH AF: 0.320

Alfa AF: 0.340 Hom.: 9915

Bravo AF: 0.309

Asia WGS AF: 0.254 AC: 887 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	2.2
DANN	Benign	0.74

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: rs2053053; hg19: chr5-149609393;