rs2053053

Variant names:

• chr5-150229830-G-A
• rs2053053
• NM_015981.4:c.1142+1475C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150229830-G-A
• chr5-150229830-G-C

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 12 publications found

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 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 53

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 63

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
CAMK2A	NM_015981.4	c.1142+1475C>T		intron_variant	Intron 16 of 18	ENST00000671881.1	NP_057065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2A	ENST00000671881.1	c.1142+1475C>T		intron_variant	Intron 16 of 18		NM_015981.4	ENSP00000500386.1

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

African (AFR) AF: 0.217 AC: 9015 AN: 41512

American (AMR) AF: 0.372 AC: 5691 AN: 15294

Ashkenazi Jewish (ASJ) AF: 0.292 AC: 1012 AN: 3470

East Asian (EAS) AF: 0.168 AC: 872 AN: 5176

South Asian (SAS) AF: 0.334 AC: 1608 AN: 4816

European-Finnish (FIN) AF: 0.320 AC: 3384 AN: 10582

Middle Eastern (MID) AF: 0.339 AC: 99 AN: 292

European-Non Finnish (NFE) AF: 0.361 AC: 24512 AN: 67982

Other (OTH) AF: 0.320 AC: 677 AN: 2114

Alfa AF: 0.338 Hom.: 12347

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
PhyloP100		0.012
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2053053; hg19: chr5-149609393;