rs17531554

Variant names:

• chr4-113583005-C-T
• rs17531554
• NM_001321571.2:c.275+26147G>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.275+26147G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.124 in 152,250 control chromosomes in the GnomAD database, including 1,403 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 0.12 (1403 hom., cov: 33)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.177
• Publications: 4 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=-0.67).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.172 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.275+26147G>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.275+26147G>A		intron_variant	Intron 4 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.124 AC: 18913 AN: 152132 Hom.: 1404 Cov.: 33

Gnomad AFR AF: 0.0506

Gnomad AMI AF: 0.123

Gnomad AMR AF: 0.0996

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0216

Gnomad SAS AF: 0.163

Gnomad FIN AF: 0.152

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.174

Gnomad OTH AF: 0.131

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

GnomAD4 genome AF: 0.124 AC: 18906 AN: 152250 Hom.: 1403 Cov.: 33 AF XY: 0.122 AC XY: 9114 AN XY: 74436

African (AFR) AF: 0.0505 AC: 2099 AN: 41558

American (AMR) AF: 0.0994 AC: 1520 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 514 AN: 3472

East Asian (EAS) AF: 0.0216 AC: 112 AN: 5176

South Asian (SAS) AF: 0.161 AC: 780 AN: 4830

European-Finnish (FIN) AF: 0.152 AC: 1614 AN: 10606

Middle Eastern (MID) AF: 0.119 AC: 35 AN: 294

European-Non Finnish (NFE) AF: 0.174 AC: 11844 AN: 67994

Other (OTH) AF: 0.130 AC: 276 AN: 2116

Alfa AF: 0.139 Hom.: 283

Bravo AF: 0.114

Asia WGS AF: 0.0910 AC: 316 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.67
CADD	Benign	11
DANN	Benign	0.76
PhyloP100		0.18
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: rs17531554; hg19: chr4-114504161;