rs17046113

Variant names:

• chr4-113504470-A-G
• rs17046113
• NM_001321571.2:c.1044+506T>C

Variant summary

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

The NM_001321571.2(CAMK2D):​c.1044+506T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.028 in 152,342 control chromosomes in the GnomAD database, including 171 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 0.028 (171 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.192
• 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

ENSG00000308709 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.5).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0939 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.1044+506T>C		intron	N/A	NP_001308500.1
	CAMK2D	NM_001321569.2		c.1044+506T>C		intron	N/A	NP_001308498.1
	CAMK2D	NM_001321573.2		c.1018-1493T>C		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.1044+506T>C		intron	N/A	ENSP00000425824.1
	CAMK2D	ENST00000394522.7	TSL:1	c.985-1493T>C		intron	N/A	ENSP00000378030.3
	CAMK2D	ENST00000508738.5	TSL:1	c.1017+3766T>C		intron	N/A	ENSP00000422566.1

Frequencies

GnomAD3 genomes AF: 0.0278 AC: 4238 AN: 152224 Hom.: 169 Cov.: 32

Gnomad AFR AF: 0.0960

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0113

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000617

Gnomad OTH AF: 0.0201

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

GnomAD4 genome AF: 0.0280 AC: 4262 AN: 152342 Hom.: 171 Cov.: 32 AF XY: 0.0276 AC XY: 2056 AN XY: 74508

African (AFR) AF: 0.0963 AC: 4004 AN: 41560

American (AMR) AF: 0.0112 AC: 171 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5190

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10626

Middle Eastern (MID) AF: 0.00680 AC: 2 AN: 294

European-Non Finnish (NFE) AF: 0.000617 AC: 42 AN: 68036

Other (OTH) AF: 0.0198 AC: 42 AN: 2116

Alfa AF: 0.0187 Hom.: 40

Bravo AF: 0.0326

Asia WGS AF: 0.00751 AC: 26 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.50
CADD	Benign	16
DANN	Benign	0.68
PhyloP100		0.19
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: rs17046113; hg19: chr4-114425626;