4-113526035-G-A

Variant names:

• chr4-113526035-G-A
• rs4834349
• NM_001321571.2:c.601+5181C>T

Variant summary

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

The NM_001321569.2(CAMK2D):​c.601+5181C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.777 in 152,158 control chromosomes in the GnomAD database, including 47,073 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 0.78 (47073 hom., cov: 32)
• Consequence: CAMK2D NM_001321569.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.230
• Publications: 1 publications found

Genes affected

CAMK2D (HGNC:1462): (calcium/calmodulin dependent protein kinase II delta) The product of this gene belongs to the serine/threonine protein kinase family and to the Ca(2+)/calmodulin-dependent protein kinase subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. In mammalian cells, the enzyme is composed of four different chains: alpha, beta, gamma, and delta. The product of this gene is a delta chain. Alternative splicing results in multiple transcript variants encoding distinct isoforms. Distinct isoforms of this chain have different expression patterns.[provided by RefSeq, Nov 2008]

CAMK2D Gene-Disease associations (from GenCC):

• CAMK2D-related neurodevelopmental disorder and dilated cardiomyopathy

  Inheritance: AD Classification: MODERATE Submitted by: G2P
• complex neurodevelopmental disorder

  Inheritance: AD Classification: MODERATE Submitted by: Ambry Genetics

ENSG00000308709 (HGNC:58873):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.94 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321569.2. 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
	CAMK2D	NM_001321571.2	MANE Select	c.601+5181C>T		intron	N/A	NP_001308500.1
	CAMK2D	NM_001321569.2		c.601+5181C>T		intron	N/A	NP_001308498.1
	CAMK2D	NM_001321573.2		c.601+5181C>T		intron	N/A	NP_001308502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2D	ENST00000511664.6	TSL:2 MANE Select	c.601+5181C>T		intron	N/A	ENSP00000425824.1
	CAMK2D	ENST00000394522.7	TSL:1	c.601+5181C>T		intron	N/A	ENSP00000378030.3
	CAMK2D	ENST00000508738.5	TSL:1	c.601+5181C>T		intron	N/A	ENSP00000422566.1

Frequencies

GnomAD3 genomes AF: 0.777 AC: 118123 AN: 152040 Hom.: 47009 Cov.: 32

Gnomad AFR AF: 0.948

Gnomad AMI AF: 0.424

Gnomad AMR AF: 0.831

Gnomad ASJ AF: 0.774

Gnomad EAS AF: 0.671

Gnomad SAS AF: 0.765

Gnomad FIN AF: 0.636

Gnomad MID AF: 0.772

Gnomad NFE AF: 0.697

Gnomad OTH AF: 0.772

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

GnomAD4 genome AF: 0.777 AC: 118248 AN: 152158 Hom.: 47073 Cov.: 32 AF XY: 0.775 AC XY: 57647 AN XY: 74376

African (AFR) AF: 0.948 AC: 39388 AN: 41544

American (AMR) AF: 0.831 AC: 12699 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.774 AC: 2689 AN: 3472

East Asian (EAS) AF: 0.671 AC: 3471 AN: 5174

South Asian (SAS) AF: 0.765 AC: 3688 AN: 4820

European-Finnish (FIN) AF: 0.636 AC: 6722 AN: 10574

Middle Eastern (MID) AF: 0.762 AC: 224 AN: 294

European-Non Finnish (NFE) AF: 0.697 AC: 47347 AN: 67976

Other (OTH) AF: 0.773 AC: 1634 AN: 2114

Alfa AF: 0.730 Hom.: 11408

Bravo AF: 0.800

Asia WGS AF: 0.749 AC: 2606 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.2
DANN	Benign	0.67
PhyloP100		-0.23
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: rs4834349; hg19: chr4-114447191;