4-113453657-C-T

Variant names:

• chr4-113453657-C-T
• rs17046072
• NM_001321571.2:c.*888G>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.*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
• Publications: 11 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:58873):

ACMG classification

Our verdict: Benign. The variant received -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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2D	NM_001321571.2	MANE Select	c.*888G>A		3_prime_UTR	Exon 21 of 21	NP_001308500.1	E9PF82
	CAMK2D	NM_001321569.2		c.*888G>A		3_prime_UTR	Exon 21 of 21	NP_001308498.1
	CAMK2D	NM_001321573.2		c.*888G>A		3_prime_UTR	Exon 21 of 21	NP_001308502.1	Q13557-11

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2D	ENST00000511664.6	TSL:2 MANE Select	c.*888G>A		3_prime_UTR	Exon 21 of 21	ENSP00000425824.1	E9PF82
	CAMK2D	ENST00000867799.1		c.*888G>A		3_prime_UTR	Exon 21 of 21	ENSP00000537858.1
	CAMK2D	ENST00000947057.1		c.*888G>A		3_prime_UTR	Exon 21 of 21	ENSP00000617116.1

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

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

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: 0.143 AC: 14 AN: 98

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AC: 0 AN: 0

Other (OTH) AF: 0.00 AC: 0 AN: 2

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

African (AFR) AF: 0.138 AC: 5724 AN: 41460

American (AMR) AF: 0.131 AC: 1996 AN: 15244

Ashkenazi Jewish (ASJ) AF: 0.148 AC: 513 AN: 3470

East Asian (EAS) AF: 0.0802 AC: 415 AN: 5172

South Asian (SAS) AF: 0.114 AC: 550 AN: 4812

European-Finnish (FIN) AF: 0.136 AC: 1440 AN: 10558

Middle Eastern (MID) AF: 0.201 AC: 59 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13160 AN: 67938

Other (OTH) AF: 0.157 AC: 330 AN: 2106

Alfa AF: 0.177 Hom.: 3398

Bravo AF: 0.159

Asia WGS AF: 0.0980 AC: 343 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.4
DANN	Benign	0.33
PhyloP100		-0.071
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: rs17046072; hg19: chr4-114374813; COSMIC: COSV105171030; COSMIC: COSV105171030;