4-113555021-C-T

Variant names:

• chr4-113555021-C-T
• rs2051785
• NM_001321571.2:c.276-2925G>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.276-2925G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.784 in 151,980 control chromosomes in the GnomAD database, including 47,072 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 (47072 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.47
• Publications: 5 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=-0.99).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.857 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.276-2925G>A		intron_variant	Intron 4 of 20	ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.276-2925G>A		intron_variant	Intron 4 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.784 AC: 119064 AN: 151862 Hom.: 47013 Cov.: 32

Gnomad AFR AF: 0.864

Gnomad AMI AF: 0.503

Gnomad AMR AF: 0.832

Gnomad ASJ AF: 0.773

Gnomad EAS AF: 0.698

Gnomad SAS AF: 0.747

Gnomad FIN AF: 0.710

Gnomad MID AF: 0.741

Gnomad NFE AF: 0.750

Gnomad OTH AF: 0.779

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

GnomAD4 genome AF: 0.784 AC: 119181 AN: 151980 Hom.: 47072 Cov.: 32 AF XY: 0.781 AC XY: 58020 AN XY: 74250

African (AFR) AF: 0.865 AC: 35867 AN: 41476

American (AMR) AF: 0.833 AC: 12714 AN: 15272

Ashkenazi Jewish (ASJ) AF: 0.773 AC: 2682 AN: 3470

East Asian (EAS) AF: 0.698 AC: 3609 AN: 5170

South Asian (SAS) AF: 0.746 AC: 3598 AN: 4820

European-Finnish (FIN) AF: 0.710 AC: 7445 AN: 10488

Middle Eastern (MID) AF: 0.735 AC: 216 AN: 294

European-Non Finnish (NFE) AF: 0.750 AC: 50947 AN: 67968

Other (OTH) AF: 0.779 AC: 1646 AN: 2114

Alfa AF: 0.766 Hom.: 83670

Bravo AF: 0.798

Asia WGS AF: 0.765 AC: 2659 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	0.064
DANN	Benign	0.32
PhyloP100		-1.5
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: rs2051785; hg19: chr4-114476177;