chr4-113710191-T-C

Variant names:

• chr4-113710191-T-C
• rs2040742
• NM_001321571.2:c.161-48419A>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.161-48419A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.175 in 152,054 control chromosomes in the GnomAD database, including 4,257 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 0.17 (4257 hom., cov: 28)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.02
• Publications: 5 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=-0.75).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.42 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2D	NM_001321571.2	c.161-48419A>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.161-48419A>G		intron_variant	Intron 2 of 20	2	NM_001321571.2	ENSP00000425824.1

Frequencies

GnomAD3 genomes AF: 0.174 AC: 26506 AN: 151936 Hom.: 4245 Cov.: 28

Gnomad AFR AF: 0.425

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.0947

Gnomad ASJ AF: 0.103

Gnomad EAS AF: 0.0251

Gnomad SAS AF: 0.141

Gnomad FIN AF: 0.0535

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.0788

Gnomad OTH AF: 0.168

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

GnomAD4 genome AF: 0.175 AC: 26564 AN: 152054 Hom.: 4257 Cov.: 28 AF XY: 0.172 AC XY: 12760 AN XY: 74324

African (AFR) AF: 0.425 AC: 17606 AN: 41432

American (AMR) AF: 0.0944 AC: 1441 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.103 AC: 358 AN: 3464

East Asian (EAS) AF: 0.0251 AC: 130 AN: 5170

South Asian (SAS) AF: 0.142 AC: 684 AN: 4826

European-Finnish (FIN) AF: 0.0535 AC: 568 AN: 10610

Middle Eastern (MID) AF: 0.122 AC: 36 AN: 294

European-Non Finnish (NFE) AF: 0.0788 AC: 5355 AN: 67976

Other (OTH) AF: 0.171 AC: 361 AN: 2108

Alfa AF: 0.106 Hom.: 2483

Bravo AF: 0.187

Asia WGS AF: 0.117 AC: 410 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.75
CADD	Benign	0.27
DANN	Benign	0.83
PhyloP100		-1.0
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: rs2040742; hg19: chr4-114631347;