rs3733619

chr4-113452099-A-Gchr4-113452099-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001321571.2(CAMK2D):c.*2446T>C variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 150,530 control chromosomes in the GnomAD database, including 1,671 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 0.14 (1671 hom., cov: 29)
  • Exomes 𝑓: 0.0 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: CAMK2D NM_001321571.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.539

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.221 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2D	NM_001321571.2	c.*2446T>C		3_prime_UTR_variant	21/21	ENST00000511664.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2D	ENST00000511664.6	c.*2446T>C		3_prime_UTR_variant	21/21	2	NM_001321571.2

Frequencies

GnomAD3 genomes AF: 0.137 AC: 20634 AN: 150410 Hom.: 1666 Cov.: 29

Gnomad AFR AF: 0.225

Gnomad AMI AF: 0.0844

Gnomad AMR AF: 0.115

Gnomad ASJ AF: 0.0983

Gnomad EAS AF: 0.0868

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.0824

Gnomad MID AF: 0.156

Gnomad NFE AF: 0.106

Gnomad OTH AF: 0.142

GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.00 AC XY: 0 AN XY: 6

Gnomad4 AFR exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.137 AC: 20661 AN: 150530 Hom.: 1671 Cov.: 29 AF XY: 0.135 AC XY: 9909 AN XY: 73432

Gnomad4 AFR AF: 0.225

Gnomad4 AMR AF: 0.114

Gnomad4 ASJ AF: 0.0983

Gnomad4 EAS AF: 0.0870

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.0824

Gnomad4 NFE AF: 0.106

Gnomad4 OTH AF: 0.143

Alfa AF: 0.117 Hom.: 1530

Bravo AF: 0.145

Asia WGS AF: 0.121 AC: 419 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	3.1
Dann	Benign	0.39

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

Publications

LitVar

Other links and lift over

dbSNP: rs3733619; hg19: chr4-114373255;