4-113705030-C-T

Variant names:

• chr4-113705030-C-T
• rs6533711
• NM_001321571.2:c.161-43258G>A

Variant summary

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

The NM_001321571.2(CAMK2D):​c.161-43258G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 151,594 control chromosomes in the GnomAD database, including 36,702 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 0.69 (36702 hom., cov: 28)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.173
• Publications: 2 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.793 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.161-43258G>A		intron	N/A	NP_001308500.1
	CAMK2D	NM_001321569.2		c.161-43258G>A		intron	N/A	NP_001308498.1
	CAMK2D	NM_001321573.2		c.161-43258G>A		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.161-43258G>A		intron	N/A	ENSP00000425824.1
	CAMK2D	ENST00000394522.7	TSL:1	c.161-43258G>A		intron	N/A	ENSP00000378030.3
	CAMK2D	ENST00000508738.5	TSL:1	c.161-43258G>A		intron	N/A	ENSP00000422566.1

Frequencies

GnomAD3 genomes AF: 0.690 AC: 104496 AN: 151476 Hom.: 36639 Cov.: 28

Gnomad AFR AF: 0.800

Gnomad AMI AF: 0.671

Gnomad AMR AF: 0.714

Gnomad ASJ AF: 0.634

Gnomad EAS AF: 0.748

Gnomad SAS AF: 0.653

Gnomad FIN AF: 0.725

Gnomad MID AF: 0.671

Gnomad NFE AF: 0.614

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.690 AC: 104624 AN: 151594 Hom.: 36702 Cov.: 28 AF XY: 0.696 AC XY: 51548 AN XY: 74054

African (AFR) AF: 0.801 AC: 33103 AN: 41352

American (AMR) AF: 0.715 AC: 10887 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.634 AC: 2197 AN: 3466

East Asian (EAS) AF: 0.749 AC: 3840 AN: 5124

South Asian (SAS) AF: 0.654 AC: 3126 AN: 4778

European-Finnish (FIN) AF: 0.725 AC: 7592 AN: 10478

Middle Eastern (MID) AF: 0.660 AC: 194 AN: 294

European-Non Finnish (NFE) AF: 0.614 AC: 41645 AN: 67858

Other (OTH) AF: 0.680 AC: 1431 AN: 2104

Alfa AF: 0.641 Hom.: 103663

Bravo AF: 0.695

Asia WGS AF: 0.728 AC: 2535 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	1.1
DANN	Benign	0.86
PhyloP100		-0.17
Mutation Taster		=99/1	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: rs6533711; hg19: chr4-114626186;