rs3776823

Variant names:

• chr5-150258042-G-A
• rs3776823
• NM_015981.4:c.218-425C>T

Your query was ambiguous. Multiple possible variants found:

• chr5-150258042-G-A
• chr5-150258042-G-C
• chr5-150258042-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_015981.4(CAMK2A):​c.218-425C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.28 in 152,086 control chromosomes in the GnomAD database, including 6,116 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 0.28 (6116 hom., cov: 33)
• Consequence: CAMK2A NM_015981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.430
• Publications: 1 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=-0.83).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.417 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2A	NM_015981.4	c.218-425C>T		intron_variant	Intron 3 of 18	ENST00000671881.1	NP_057065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2A	ENST00000671881.1	c.218-425C>T		intron_variant	Intron 3 of 18		NM_015981.4	ENSP00000500386.1

Frequencies

GnomAD3 genomes AF: 0.280 AC: 42617 AN: 151968 Hom.: 6120 Cov.: 33

Gnomad AFR AF: 0.268

Gnomad AMI AF: 0.198

Gnomad AMR AF: 0.314

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.434

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.264

Gnomad NFE AF: 0.281

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.280 AC: 42649 AN: 152086 Hom.: 6116 Cov.: 33 AF XY: 0.279 AC XY: 20714 AN XY: 74348

African (AFR) AF: 0.268 AC: 11111 AN: 41486

American (AMR) AF: 0.314 AC: 4801 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.204 AC: 708 AN: 3470

East Asian (EAS) AF: 0.323 AC: 1670 AN: 5168

South Asian (SAS) AF: 0.433 AC: 2082 AN: 4812

European-Finnish (FIN) AF: 0.222 AC: 2344 AN: 10574

Middle Eastern (MID) AF: 0.257 AC: 75 AN: 292

European-Non Finnish (NFE) AF: 0.281 AC: 19094 AN: 67980

Other (OTH) AF: 0.276 AC: 583 AN: 2114

Alfa AF: 0.271 Hom.: 818

Bravo AF: 0.283

Asia WGS AF: 0.352 AC: 1227 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	2.6
DANN	Benign	0.69
PhyloP100		-0.43
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: rs3776823; hg19: chr5-149637605;