rs144277535

Variant names:

• chr4-113515168-C-T
• rs144277535
• NM_001321571.2:c.720G>A

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4_Strong BP6_Very_Strong BP7 BS2

The NM_001321571.2(CAMK2D):​c.720G>A​(p.Thr240Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000398 in 1,604,964 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0022 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00021 (2 hom.)
• Consequence: CAMK2D NM_001321571.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -4.85
• Publications: 0 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 -17 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 4-113515168-C-T is Benign according to our data. Variant chr4-113515168-C-T is described in ClinVar as Benign. ClinVar VariationId is 711414.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-4.85 with no splicing effect.
• BS2: High AC in GnomAd4 at 327 AD gene.

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.720G>A	p.Thr240Thr	synonymous	Exon 10 of 21	NP_001308500.1	E9PF82
	CAMK2D	NM_001321569.2		c.720G>A	p.Thr240Thr	synonymous	Exon 10 of 21	NP_001308498.1
	CAMK2D	NM_001321573.2		c.720G>A	p.Thr240Thr	synonymous	Exon 10 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.720G>A	p.Thr240Thr	synonymous	Exon 10 of 21	ENSP00000425824.1	E9PF82
	CAMK2D	ENST00000394522.7	TSL:1	c.720G>A	p.Thr240Thr	synonymous	Exon 10 of 18	ENSP00000378030.3	Q13557-10
	CAMK2D	ENST00000508738.5	TSL:1	c.720G>A	p.Thr240Thr	synonymous	Exon 10 of 18	ENSP00000422566.1	Q13557-9

Frequencies

GnomAD3 genomes AF: 0.00215 AC: 327 AN: 151964 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00696

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00190

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000208

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00288

GnomAD2 exomes AF: 0.000533 AC: 132 AN: 247612 AF XY: 0.000456

Gnomad AFR exome AF: 0.00705

Gnomad AMR exome AF: 0.000298

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000355

Gnomad OTH exome AF: 0.000166

GnomAD4 exome AF: 0.000215 AC: 312 AN: 1452882 Hom.: 2 Cov.: 28 AF XY: 0.000185 AC XY: 134 AN XY: 722678

African (AFR) AF: 0.00721 AC: 239 AN: 33138

American (AMR) AF: 0.000436 AC: 19 AN: 43596

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25950

East Asian (EAS) AF: 0.00 AC: 0 AN: 39494

South Asian (SAS) AF: 0.0000830 AC: 7 AN: 84304

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53222

Middle Eastern (MID) AF: 0.000175 AC: 1 AN: 5730

European-Non Finnish (NFE) AF: 0.0000135 AC: 15 AN: 1107400

Other (OTH) AF: 0.000516 AC: 31 AN: 60048

GnomAD4 genome AF: 0.00215 AC: 327 AN: 152082 Hom.: 0 Cov.: 32 AF XY: 0.00202 AC XY: 150 AN XY: 74344

African (AFR) AF: 0.00694 AC: 288 AN: 41498

American (AMR) AF: 0.00190 AC: 29 AN: 15258

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5182

South Asian (SAS) AF: 0.000209 AC: 1 AN: 4794

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10568

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.0000441 AC: 3 AN: 68004

Other (OTH) AF: 0.00285 AC: 6 AN: 2106

Alfa AF: 0.00114 Hom.: 1

Bravo AF: 0.00274

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	4.4
DANN	Benign	0.53
PhyloP100		-4.8
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.7
Mutation Taster		=99/1	polymorphism

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: rs144277535; hg19: chr4-114436324; COSMIC: COSV99592935; COSMIC: COSV99592935;