4-113511181-T-C

Variant names:

• chr4-113511181-T-C
• rs13130985
• NM_001321571.2:c.947-1506A>G

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Moderate BA1

The ENST00000511664.6(CAMK2D):​c.947-1506A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.641 in 151,972 control chromosomes in the GnomAD database, including 32,871 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 0.64 (32871 hom., cov: 32)
• Consequence: CAMK2D ENST00000511664.6 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.32
• 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

ENSG00000308709 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.3).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.843 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000511664.6. 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.947-1506A>G		intron	N/A	NP_001308500.1
	CAMK2D	NM_001321569.2		c.947-1506A>G		intron	N/A	NP_001308498.1
	CAMK2D	NM_001321573.2		c.947-1506A>G		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.947-1506A>G		intron	N/A	ENSP00000425824.1
	CAMK2D	ENST00000394522.7	TSL:1	c.947-1506A>G		intron	N/A	ENSP00000378030.3
	CAMK2D	ENST00000508738.5	TSL:1	c.947-1506A>G		intron	N/A	ENSP00000422566.1

Frequencies

GnomAD3 genomes AF: 0.641 AC: 97382 AN: 151856 Hom.: 32816 Cov.: 32

Gnomad AFR AF: 0.850

Gnomad AMI AF: 0.340

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.596

Gnomad EAS AF: 0.323

Gnomad SAS AF: 0.426

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.630

Gnomad NFE AF: 0.568

Gnomad OTH AF: 0.636

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

GnomAD4 genome AF: 0.641 AC: 97490 AN: 151972 Hom.: 32871 Cov.: 32 AF XY: 0.634 AC XY: 47086 AN XY: 74244

African (AFR) AF: 0.850 AC: 35280 AN: 41504

American (AMR) AF: 0.691 AC: 10551 AN: 15260

Ashkenazi Jewish (ASJ) AF: 0.596 AC: 2066 AN: 3468

East Asian (EAS) AF: 0.323 AC: 1668 AN: 5162

South Asian (SAS) AF: 0.426 AC: 2052 AN: 4812

European-Finnish (FIN) AF: 0.520 AC: 5485 AN: 10542

Middle Eastern (MID) AF: 0.627 AC: 183 AN: 292

European-Non Finnish (NFE) AF: 0.568 AC: 38568 AN: 67914

Other (OTH) AF: 0.630 AC: 1328 AN: 2108

Alfa AF: 0.604 Hom.: 3384

Bravo AF: 0.669

Asia WGS AF: 0.386 AC: 1341 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.30
CADD	Benign	18
DANN	Benign	0.84
PhyloP100		1.3
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: rs13130985; hg19: chr4-114432337;