4-113560135-T-G

Variant names:

• chr4-113560135-T-G
• rs17630328
• NM_001321571.2:c.276-8039A>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.276-8039A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 152,108 control chromosomes in the GnomAD database, including 1,790 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 0.13 (1790 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.415
• 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=-0.97).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.297 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.276-8039A>C		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.276-8039A>C		intron_variant	Intron 4 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.132 AC: 20045 AN: 151992 Hom.: 1774 Cov.: 32

Gnomad AFR AF: 0.201

Gnomad AMI AF: 0.0780

Gnomad AMR AF: 0.200

Gnomad ASJ AF: 0.0588

Gnomad EAS AF: 0.309

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0708

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0775

Gnomad OTH AF: 0.123

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

GnomAD4 genome AF: 0.132 AC: 20102 AN: 152108 Hom.: 1790 Cov.: 32 AF XY: 0.134 AC XY: 9985 AN XY: 74358

African (AFR) AF: 0.202 AC: 8378 AN: 41490

American (AMR) AF: 0.201 AC: 3075 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.0588 AC: 204 AN: 3468

East Asian (EAS) AF: 0.309 AC: 1600 AN: 5174

South Asian (SAS) AF: 0.0997 AC: 480 AN: 4814

European-Finnish (FIN) AF: 0.0708 AC: 750 AN: 10596

Middle Eastern (MID) AF: 0.0646 AC: 19 AN: 294

European-Non Finnish (NFE) AF: 0.0775 AC: 5269 AN: 67980

Other (OTH) AF: 0.121 AC: 256 AN: 2112

Alfa AF: 0.0839 Hom.: 465

Bravo AF: 0.148

Asia WGS AF: 0.168 AC: 583 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	1.9
DANN	Benign	0.44
PhyloP100		0.41
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: rs17630328; hg19: chr4-114481291;