rs2675671

chr10-73873002-C-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Moderate BP6_Moderate BP7 BA1

The NM_001367534.1(CAMK2G):c.147G>A(p.Lys49=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.502 in 1,605,810 control chromosomes in the GnomAD database, including 214,091 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.43 (15804 hom., cov: 29)
  • Exomes 𝑓: 0.51 (198287 hom.)
• Consequence: CAMK2G NM_001367534.1 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.98

Genes affected

CAMK2G (HGNC:1463): (calcium/calmodulin dependent protein kinase II gamma) The product of this gene is one of the four subunits of an enzyme which 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 gamma chain. Many alternatively spliced transcripts encoding different isoforms have been described but the full-length nature of all the variants has not been determined.[provided by RefSeq, Mar 2011]

ACMG classification

Verdict is Benign. Variant got -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.31).
• BP6: Variant 10-73873002-C-T is Benign according to our data. Variant chr10-73873002-C-T is described in ClinVar as [Benign]. Clinvar id is 1192578.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr10-73873002-C-T is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=1.98 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.554 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
CAMK2G	NM_001367534.1	c.147G>A	p.Lys49=	synonymous_variant	2/23	ENST00000423381.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
CAMK2G	ENST00000423381.6	c.147G>A	p.Lys49=	synonymous_variant	2/23	5	NM_001367534.1

Frequencies

GnomAD3 genomes AF: 0.433 AC: 65612 AN: 151516 Hom.: 15806 Cov.: 29

Gnomad AFR AF: 0.258

Gnomad AMI AF: 0.523

Gnomad AMR AF: 0.428

Gnomad ASJ AF: 0.572

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.313

Gnomad FIN AF: 0.450

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.517

GnomAD3 exomes AF: 0.433 AC: 108915 AN: 251476 Hom.: 26986 AF XY: 0.443 AC XY: 60173 AN XY: 135910

Gnomad AFR exome AF: 0.252

Gnomad AMR exome AF: 0.296

Gnomad ASJ exome AF: 0.559

Gnomad EAS exome AF: 0.106

Gnomad SAS exome AF: 0.326

Gnomad FIN exome AF: 0.446

Gnomad NFE exome AF: 0.566

Gnomad OTH exome AF: 0.494

GnomAD4 exome AF: 0.509 AC: 740398 AN: 1454176 Hom.: 198287 Cov.: 31 AF XY: 0.507 AC XY: 367003 AN XY: 723878

Gnomad4 AFR exome AF: 0.249

Gnomad4 AMR exome AF: 0.311

Gnomad4 ASJ exome AF: 0.564

Gnomad4 EAS exome AF: 0.119

Gnomad4 SAS exome AF: 0.330

Gnomad4 FIN exome AF: 0.447

Gnomad4 NFE exome AF: 0.555

Gnomad4 OTH exome AF: 0.491

GnomAD4 genome AF: 0.433 AC: 65623 AN: 151634 Hom.: 15804 Cov.: 29 AF XY: 0.427 AC XY: 31632 AN XY: 74088

Gnomad4 AFR AF: 0.258

Gnomad4 AMR AF: 0.428

Gnomad4 ASJ AF: 0.572

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.314

Gnomad4 FIN AF: 0.450

Gnomad4 NFE AF: 0.559

Gnomad4 OTH AF: 0.512

Alfa AF: 0.536 Hom.: 44438

Bravo AF: 0.424

Asia WGS AF: 0.200 AC: 697 AN: 3478

EpiCase AF: 0.578

EpiControl AF: 0.587

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual developmental disorder 59 Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 14, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
Cadd	Benign	12
Dann	Benign	0.56

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: rs2675671; hg19: chr10-75632760; COSMIC: COSV59480719;