chr4-113505159-G-T

Variant names:

• chr4-113505159-G-T
• rs4834348
• NM_001321571.2:c.985-124C>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.985-124C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.431 in 473,122 control chromosomes in the GnomAD database, including 46,515 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 0.43 (14771 hom., cov: 30)
  • Exomes 𝑓: 0.43 (31744 hom.)
• Consequence: CAMK2D NM_001321571.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.66
• 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:58873):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.466 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.985-124C>A		intron	N/A	NP_001308500.1	E9PF82
	CAMK2D	NM_001321569.2		c.985-124C>A		intron	N/A	NP_001308498.1
	CAMK2D	NM_001321573.2		c.1018-2182C>A		intron	N/A	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.985-124C>A		intron	N/A	ENSP00000425824.1	E9PF82
	CAMK2D	ENST00000394522.7	TSL:1	c.985-2182C>A		intron	N/A	ENSP00000378030.3	Q13557-10
	CAMK2D	ENST00000508738.5	TSL:1	c.1017+3077C>A		intron	N/A	ENSP00000422566.1	Q13557-9

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65693 AN: 151774 Hom.: 14769 Cov.: 30

Gnomad AFR AF: 0.466

Gnomad AMI AF: 0.292

Gnomad AMR AF: 0.363

Gnomad ASJ AF: 0.474

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.377

Gnomad FIN AF: 0.339

Gnomad MID AF: 0.509

Gnomad NFE AF: 0.471

Gnomad OTH AF: 0.464

GnomAD4 exome AF: 0.430 AC: 138125 AN: 321230 Hom.: 31744 AF XY: 0.432 AC XY: 73522 AN XY: 169994

African (AFR) AF: 0.463 AC: 3798 AN: 8206

American (AMR) AF: 0.323 AC: 3441 AN: 10642

Ashkenazi Jewish (ASJ) AF: 0.483 AC: 5261 AN: 10888

East Asian (EAS) AF: 0.119 AC: 2853 AN: 23998

South Asian (SAS) AF: 0.398 AC: 7195 AN: 18062

European-Finnish (FIN) AF: 0.363 AC: 8619 AN: 23768

Middle Eastern (MID) AF: 0.543 AC: 1689 AN: 3110

European-Non Finnish (NFE) AF: 0.476 AC: 96607 AN: 202958

Other (OTH) AF: 0.442 AC: 8662 AN: 19598

GnomAD4 genome AF: 0.433 AC: 65718 AN: 151892 Hom.: 14771 Cov.: 30 AF XY: 0.421 AC XY: 31241 AN XY: 74258

African (AFR) AF: 0.465 AC: 19269 AN: 41400

American (AMR) AF: 0.362 AC: 5528 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.474 AC: 1644 AN: 3468

East Asian (EAS) AF: 0.104 AC: 535 AN: 5158

South Asian (SAS) AF: 0.376 AC: 1812 AN: 4816

European-Finnish (FIN) AF: 0.339 AC: 3575 AN: 10552

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.471 AC: 31970 AN: 67908

Other (OTH) AF: 0.459 AC: 970 AN: 2112

Alfa AF: 0.462 Hom.: 8646

Bravo AF: 0.436

Asia WGS AF: 0.248 AC: 863 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	14
DANN	Benign	0.71
PhyloP100		2.7
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: rs4834348; hg19: chr4-114426315; COSMIC: COSV56432167;