rs2040744

Variant names:

• chr4-113712208-A-G
• rs2040744
• NM_001321571.2:c.160+47112T>C

Your query was ambiguous. Multiple possible variants found:

• chr4-113712208-A-G
• chr4-113712208-A-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.160+47112T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.719 in 152,018 control chromosomes in the GnomAD database, including 40,323 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 0.72 (40323 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.922
• Publications: 1 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=-0.97).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.872 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.160+47112T>C		intron_variant	Intron 2 of 20	ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.160+47112T>C		intron_variant	Intron 2 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.719 AC: 109230 AN: 151900 Hom.: 40250 Cov.: 32

Gnomad AFR AF: 0.880

Gnomad AMI AF: 0.668

Gnomad AMR AF: 0.730

Gnomad ASJ AF: 0.638

Gnomad EAS AF: 0.747

Gnomad SAS AF: 0.667

Gnomad FIN AF: 0.727

Gnomad MID AF: 0.680

Gnomad NFE AF: 0.625

Gnomad OTH AF: 0.699

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

GnomAD4 genome AF: 0.719 AC: 109367 AN: 152018 Hom.: 40323 Cov.: 32 AF XY: 0.724 AC XY: 53791 AN XY: 74276

African (AFR) AF: 0.880 AC: 36511 AN: 41488

American (AMR) AF: 0.731 AC: 11130 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.638 AC: 2213 AN: 3468

East Asian (EAS) AF: 0.748 AC: 3871 AN: 5178

South Asian (SAS) AF: 0.667 AC: 3213 AN: 4814

European-Finnish (FIN) AF: 0.727 AC: 7688 AN: 10568

Middle Eastern (MID) AF: 0.670 AC: 197 AN: 294

European-Non Finnish (NFE) AF: 0.625 AC: 42456 AN: 67948

Other (OTH) AF: 0.700 AC: 1479 AN: 2112

Alfa AF: 0.629 Hom.: 2756

Bravo AF: 0.728

Asia WGS AF: 0.743 AC: 2587 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.97
CADD	Benign	1.2
DANN	Benign	0.79
PhyloP100		-0.92
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: rs2040744; hg19: chr4-114633364;