ENST00000683023.1:n.*29+14996C>T

Variant names:

• chr4-113440730-G-A
• rs7684418
• ENST00000683023.1:n.*29+14996C>T

Variant summary

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

The ENST00000683023.1(CAMK2D):​n.*29+14996C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.078 in 152,160 control chromosomes in the GnomAD database, including 501 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 0.078 (501 hom., cov: 31)
• Consequence: CAMK2D ENST00000683023.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.07
• Publications: 8 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=-0.71).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0865 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000683023.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2D	ENST00000683023.1		n.*29+14996C>T		intron	N/A	ENSP00000507073.1
	ENSG00000308709	ENST00000835919.1		n.135+33732G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.0780 AC: 11858 AN: 152042 Hom.: 501 Cov.: 31

Gnomad AFR AF: 0.0666

Gnomad AMI AF: 0.0768

Gnomad AMR AF: 0.0649

Gnomad ASJ AF: 0.0844

Gnomad EAS AF: 0.0857

Gnomad SAS AF: 0.0693

Gnomad FIN AF: 0.0718

Gnomad MID AF: 0.0949

Gnomad NFE AF: 0.0884

Gnomad OTH AF: 0.0804

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

GnomAD4 genome AF: 0.0780 AC: 11864 AN: 152160 Hom.: 501 Cov.: 31 AF XY: 0.0768 AC XY: 5712 AN XY: 74390

African (AFR) AF: 0.0667 AC: 2767 AN: 41510

American (AMR) AF: 0.0648 AC: 991 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.0844 AC: 293 AN: 3470

East Asian (EAS) AF: 0.0859 AC: 445 AN: 5182

South Asian (SAS) AF: 0.0687 AC: 331 AN: 4816

European-Finnish (FIN) AF: 0.0718 AC: 760 AN: 10590

Middle Eastern (MID) AF: 0.105 AC: 31 AN: 294

European-Non Finnish (NFE) AF: 0.0884 AC: 6009 AN: 67990

Other (OTH) AF: 0.0791 AC: 167 AN: 2112

Alfa AF: 0.0856 Hom.: 413

Bravo AF: 0.0776

Asia WGS AF: 0.0790 AC: 275 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.71
CADD	Benign	6.3
DANN	Benign	0.64
PhyloP100		2.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7684418; hg19: chr4-114361886;