rs9929

Variant names:

• chr4-113453977-C-T
• rs9929
• NM_001321571.2:c.*568G>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.*568G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0417 in 152,298 control chromosomes in the GnomAD database, including 182 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 0.042 (182 hom., cov: 31)
  • Exomes 𝑓: 0.029 (0 hom.)
• Consequence: CAMK2D NM_001321571.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.103
• 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

ENSG00000308709 (HGNC:):

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.56).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.0675 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001321571.2. 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.*568G>A		3_prime_UTR	Exon 21 of 21	NP_001308500.1
	CAMK2D	NM_001321569.2		c.*568G>A		3_prime_UTR	Exon 21 of 21	NP_001308498.1
	CAMK2D	NM_001321573.2		c.*568G>A		3_prime_UTR	Exon 21 of 21	NP_001308502.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2D	ENST00000511664.6	TSL:2 MANE Select	c.*568G>A		3_prime_UTR	Exon 21 of 21	ENSP00000425824.1
	CAMK2D	ENST00000699372.1		n.*1581G>A		non_coding_transcript_exon	Exon 18 of 18	ENSP00000514337.1
	CAMK2D	ENST00000699377.1		n.*3257G>A		non_coding_transcript_exon	Exon 19 of 19	ENSP00000514342.1

Frequencies

GnomAD3 genomes AF: 0.0417 AC: 6334 AN: 151738 Hom.: 183 Cov.: 31

Gnomad AFR AF: 0.0115

Gnomad AMI AF: 0.0735

Gnomad AMR AF: 0.0466

Gnomad ASJ AF: 0.0553

Gnomad EAS AF: 0.000386

Gnomad SAS AF: 0.0742

Gnomad FIN AF: 0.0332

Gnomad MID AF: 0.0665

Gnomad NFE AF: 0.0597

Gnomad OTH AF: 0.0500

GnomAD4 exome AF: 0.0293 AC: 13 AN: 444 Hom.: 0 Cov.: 0 AF XY: 0.0301 AC XY: 8 AN XY: 266

African (AFR) AC: 0 AN: 0

American (AMR) AF: 0.00 AC: 0 AN: 2

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.0302 AC: 13 AN: 430

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 6

Other (OTH) AF: 0.00 AC: 0 AN: 6

GnomAD4 genome AF: 0.0417 AC: 6331 AN: 151854 Hom.: 182 Cov.: 31 AF XY: 0.0407 AC XY: 3022 AN XY: 74218

African (AFR) AF: 0.0115 AC: 477 AN: 41426

American (AMR) AF: 0.0466 AC: 709 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.0553 AC: 192 AN: 3472

East Asian (EAS) AF: 0.000387 AC: 2 AN: 5168

South Asian (SAS) AF: 0.0738 AC: 355 AN: 4810

European-Finnish (FIN) AF: 0.0332 AC: 349 AN: 10510

Middle Eastern (MID) AF: 0.0714 AC: 21 AN: 294

European-Non Finnish (NFE) AF: 0.0597 AC: 4055 AN: 67932

Other (OTH) AF: 0.0495 AC: 104 AN: 2102

Alfa AF: 0.0488 Hom.: 30

Bravo AF: 0.0399

Asia WGS AF: 0.0260 AC: 90 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.56
CADD	Benign	6.8
DANN	Benign	0.73
PhyloP100		0.10
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: rs9929; hg19: chr4-114375133;