5-150258042-G-T

Variant names:

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

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_015981.4(CAMK2A):​c.218-425C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2A	NM_015981.4	MANE Select	c.218-425C>A		intron	N/A	NP_057065.2
	CAMK2A	NM_001363989.1		c.218-425C>A		intron	N/A	NP_001350918.1
	CAMK2A	NM_001363990.1		c.218-425C>A		intron	N/A	NP_001350919.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2A	ENST00000671881.1	MANE Select	c.218-425C>A		intron	N/A	ENSP00000500386.1
	CAMK2A	ENST00000348628.11	TSL:1	c.218-425C>A		intron	N/A	ENSP00000261793.8
	CAMK2A	ENST00000398376.8	TSL:1	c.218-425C>A		intron	N/A	ENSP00000381412.4

Frequencies

GnomAD3 genomes Cov.: 33

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

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	2.3
DANN	Benign	0.75
PhyloP100		-0.43

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;