rs4834340

Variant names:

• chr4-113479513-G-A
• rs4834340
• NM_001321571.2:c.1136-13909C>T

Variant summary

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

The NM_001321571.2(CAMK2D):​c.1136-13909C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.34 in 151,988 control chromosomes in the GnomAD database, including 9,108 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 0.34 (9108 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.00
• Publications: 9 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:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.97).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.372 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321571.2. 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.1136-13909C>T		intron	N/A	NP_001308500.1
	CAMK2D	NM_001321569.2		c.1136-13909C>T		intron	N/A	NP_001308498.1
	CAMK2D	NM_001321573.2		c.1109-13909C>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.1136-13909C>T		intron	N/A	ENSP00000425824.1
	CAMK2D	ENST00000394522.7	TSL:1	c.1076-13909C>T		intron	N/A	ENSP00000378030.3
	CAMK2D	ENST00000508738.5	TSL:1	c.1067-13909C>T		intron	N/A	ENSP00000422566.1

Frequencies

GnomAD3 genomes AF: 0.340 AC: 51665 AN: 151868 Hom.: 9101 Cov.: 32

Gnomad AFR AF: 0.359

Gnomad AMI AF: 0.275

Gnomad AMR AF: 0.289

Gnomad ASJ AF: 0.308

Gnomad EAS AF: 0.0836

Gnomad SAS AF: 0.233

Gnomad FIN AF: 0.297

Gnomad MID AF: 0.401

Gnomad NFE AF: 0.376

Gnomad OTH AF: 0.352

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

GnomAD4 genome AF: 0.340 AC: 51700 AN: 151988 Hom.: 9108 Cov.: 32 AF XY: 0.331 AC XY: 24598 AN XY: 74286

African (AFR) AF: 0.359 AC: 14889 AN: 41446

American (AMR) AF: 0.289 AC: 4407 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.308 AC: 1070 AN: 3472

East Asian (EAS) AF: 0.0836 AC: 433 AN: 5178

South Asian (SAS) AF: 0.233 AC: 1124 AN: 4818

European-Finnish (FIN) AF: 0.297 AC: 3135 AN: 10560

Middle Eastern (MID) AF: 0.401 AC: 117 AN: 292

European-Non Finnish (NFE) AF: 0.376 AC: 25542 AN: 67942

Other (OTH) AF: 0.348 AC: 732 AN: 2104

Alfa AF: 0.357 Hom.: 5656

Bravo AF: 0.342

Asia WGS AF: 0.168 AC: 585 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	0.21
DANN	Benign	0.54
PhyloP100		-1.0
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: rs4834340; hg19: chr4-114400669;