rs7697831

Variant names:

• chr4-113506649-G-A
• rs7697831
• NM_001321571.2:c.985-1614C>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.985-1614C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,032 control chromosomes in the GnomAD database, including 3,498 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 0.21 (3498 hom., cov: 32)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.356
• Publications: 3 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=-0.85).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.985-1614C>T		intron_variant	Intron 13 of 20	ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.985-1614C>T		intron_variant	Intron 13 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31429 AN: 151914 Hom.: 3492 Cov.: 32

Gnomad AFR AF: 0.252

Gnomad AMI AF: 0.101

Gnomad AMR AF: 0.183

Gnomad ASJ AF: 0.257

Gnomad EAS AF: 0.0206

Gnomad SAS AF: 0.243

Gnomad FIN AF: 0.0978

Gnomad MID AF: 0.263

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.231

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

GnomAD4 genome AF: 0.207 AC: 31454 AN: 152032 Hom.: 3498 Cov.: 32 AF XY: 0.200 AC XY: 14867 AN XY: 74324

African (AFR) AF: 0.252 AC: 10460 AN: 41450

American (AMR) AF: 0.183 AC: 2791 AN: 15270

Ashkenazi Jewish (ASJ) AF: 0.257 AC: 891 AN: 3462

East Asian (EAS) AF: 0.0207 AC: 107 AN: 5176

South Asian (SAS) AF: 0.242 AC: 1164 AN: 4816

European-Finnish (FIN) AF: 0.0978 AC: 1034 AN: 10578

Middle Eastern (MID) AF: 0.276 AC: 81 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14346 AN: 67964

Other (OTH) AF: 0.231 AC: 488 AN: 2112

Alfa AF: 0.219 Hom.: 2354

Bravo AF: 0.212

Asia WGS AF: 0.143 AC: 496 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	6.1
DANN	Benign	0.68
PhyloP100		0.36
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: rs7697831; hg19: chr4-114427805;