NM_001321571.2:c.161-1883A>G

Variant names:

• chr4-113663655-T-C
• rs13107662
• NM_001321571.2:c.161-1883A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321571.2(CAMK2D):​c.161-1883A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.275 in 149,910 control chromosomes in the GnomAD database, including 6,532 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 0.27 (6532 hom., cov: 31)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.246
• 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=-0.82).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.161-1883A>G		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.161-1883A>G		intron_variant	Intron 2 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.275 AC: 41236 AN: 149880 Hom.: 6539 Cov.: 31

Gnomad AFR AF: 0.119

Gnomad AMI AF: 0.437

Gnomad AMR AF: 0.325

Gnomad ASJ AF: 0.329

Gnomad EAS AF: 0.281

Gnomad SAS AF: 0.398

Gnomad FIN AF: 0.346

Gnomad MID AF: 0.244

Gnomad NFE AF: 0.335

Gnomad OTH AF: 0.272

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

GnomAD4 genome AF: 0.275 AC: 41219 AN: 149910 Hom.: 6532 Cov.: 31 AF XY: 0.279 AC XY: 20432 AN XY: 73154

African (AFR) AF: 0.119 AC: 4892 AN: 41038

American (AMR) AF: 0.324 AC: 4860 AN: 14998

Ashkenazi Jewish (ASJ) AF: 0.329 AC: 1137 AN: 3460

East Asian (EAS) AF: 0.280 AC: 1440 AN: 5142

South Asian (SAS) AF: 0.397 AC: 1887 AN: 4748

European-Finnish (FIN) AF: 0.346 AC: 3354 AN: 9680

Middle Eastern (MID) AF: 0.241 AC: 69 AN: 286

European-Non Finnish (NFE) AF: 0.335 AC: 22618 AN: 67582

Other (OTH) AF: 0.273 AC: 566 AN: 2070

Alfa AF: 0.317 Hom.: 15232

Bravo AF: 0.264

Asia WGS AF: 0.348 AC: 1204 AN: 3450

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	3.0
DANN	Benign	0.84
PhyloP100		0.25
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: rs13107662; hg19: chr4-114584811;