4-113453657-C-T

Position:

• chr4-113453657-C-T

Variant summary

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

The NM_001321571.2(CAMK2D):​c.*888G>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 0.16 in 152,066 control chromosomes in the GnomAD database, including 1,994 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 0.16 (1994 hom., cov: 32)
  • Exomes 𝑓: 0.14 (0 hom.)
• Consequence: CAMK2D NM_001321571.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0710

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=-0.81).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.191 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.*888G>A		3_prime_UTR_variant	21/21	ENST00000511664.6	NP_001308500.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CAMK2D	ENST00000511664.6	c.*888G>A		3_prime_UTR_variant	21/21	2	NM_001321571.2	ENSP00000425824

Frequencies

GnomAD3 genomes AF: 0.160 AC: 24241 AN: 151848 Hom.: 1988 Cov.: 32

Gnomad AFR AF: 0.138

Gnomad AMI AF: 0.0932

Gnomad AMR AF: 0.131

Gnomad ASJ AF: 0.148

Gnomad EAS AF: 0.0802

Gnomad SAS AF: 0.114

Gnomad FIN AF: 0.136

Gnomad MID AF: 0.206

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.160

GnomAD4 exome AF: 0.140 AC: 14 AN: 100 Hom.: 0 Cov.: 0 AF XY: 0.108 AC XY: 8 AN XY: 74

Gnomad4 FIN exome AF: 0.143

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.160 AC: 24272 AN: 151966 Hom.: 1994 Cov.: 32 AF XY: 0.154 AC XY: 11471 AN XY: 74276

Gnomad4 AFR AF: 0.138

Gnomad4 AMR AF: 0.131

Gnomad4 ASJ AF: 0.148

Gnomad4 EAS AF: 0.0802

Gnomad4 SAS AF: 0.114

Gnomad4 FIN AF: 0.136

Gnomad4 NFE AF: 0.194

Gnomad4 OTH AF: 0.157

Alfa AF: 0.173 Hom.: 2146

Bravo AF: 0.159

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.33

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: rs17046072; hg19: chr4-114374813; COSMIC: COSV105171030; COSMIC: COSV105171030;