5-150243802-C-T

Variant names:

• chr5-150243802-C-T
• rs4958456
• NM_015981.4:c.984+1359G>A

Variant summary

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

The NM_015981.4(CAMK2A):​c.984+1359G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.136 in 152,128 control chromosomes in the GnomAD database, including 1,597 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 0.14 (1597 hom., cov: 32)
• Consequence: CAMK2A NM_015981.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.377
• Publications: 17 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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.333 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_015981.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2A	NM_015981.4	MANE Select	c.984+1359G>A		intron	N/A	NP_057065.2
	CAMK2A	NM_001363989.1		c.984+1359G>A		intron	N/A	NP_001350918.1
	CAMK2A	NM_001363990.1		c.984+1359G>A		intron	N/A	NP_001350919.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2A	ENST00000671881.1	MANE Select	c.984+1359G>A		intron	N/A	ENSP00000500386.1
	CAMK2A	ENST00000348628.11	TSL:1	c.984+1359G>A		intron	N/A	ENSP00000261793.8
	CAMK2A	ENST00000398376.8	TSL:1	c.984+1359G>A		intron	N/A	ENSP00000381412.4

Frequencies

GnomAD3 genomes AF: 0.136 AC: 20668 AN: 152010 Hom.: 1594 Cov.: 32

Gnomad AFR AF: 0.100

Gnomad AMI AF: 0.215

Gnomad AMR AF: 0.112

Gnomad ASJ AF: 0.112

Gnomad EAS AF: 0.347

Gnomad SAS AF: 0.252

Gnomad FIN AF: 0.125

Gnomad MID AF: 0.0570

Gnomad NFE AF: 0.142

Gnomad OTH AF: 0.109

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

GnomAD4 genome AF: 0.136 AC: 20691 AN: 152128 Hom.: 1597 Cov.: 32 AF XY: 0.137 AC XY: 10197 AN XY: 74362

African (AFR) AF: 0.101 AC: 4175 AN: 41510

American (AMR) AF: 0.113 AC: 1724 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.112 AC: 390 AN: 3470

East Asian (EAS) AF: 0.346 AC: 1787 AN: 5164

South Asian (SAS) AF: 0.251 AC: 1206 AN: 4814

European-Finnish (FIN) AF: 0.125 AC: 1326 AN: 10580

Middle Eastern (MID) AF: 0.0578 AC: 17 AN: 294

European-Non Finnish (NFE) AF: 0.142 AC: 9632 AN: 67980

Other (OTH) AF: 0.113 AC: 238 AN: 2114

Alfa AF: 0.136 Hom.: 4977

Bravo AF: 0.129

Asia WGS AF: 0.286 AC: 994 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
CADD	Benign	4.5
DANN	Benign	0.56
PhyloP100		-0.38
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: rs4958456; hg19: chr5-149623365;