rs2675671

Variant names:

• chr10-73873002-C-T
• rs2675671
• NM_001367534.1:c.147G>A

Variant summary

Our verdict is Benign. The variant received -19 ACMG points: 0P and 19B. BP4_Moderate BP6_Very_Strong BP7 BA1

The NM_001367534.1(CAMK2G):​c.147G>A​(p.Lys49Lys) 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, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.98
• Publications: 40 publications found

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]

CAMK2G Gene-Disease associations (from GenCC):

• intellectual developmental disorder 59

  Inheritance: AD Classification: STRONG, LIMITED Submitted by: ClinGen, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P, Illumina
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -19 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 VariationId is 1192578.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• 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 rank	MANE	Protein	UniProt
CAMK2G	NM_001367534.1	c.147G>A	p.Lys49Lys	synonymous_variant	Exon 2 of 23	ENST00000423381.6	NP_001354463.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2G	ENST00000423381.6	c.147G>A	p.Lys49Lys	synonymous_variant	Exon 2 of 23	5	NM_001367534.1	ENSP00000410298.3

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

GnomAD2 exomes AF: 0.433 AC: 108915 AN: 251476 AF XY: 0.443

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 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

African (AFR) AF: 0.249 AC: 8319 AN: 33382

American (AMR) AF: 0.311 AC: 13924 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 14732 AN: 26100

East Asian (EAS) AF: 0.119 AC: 4712 AN: 39688

South Asian (SAS) AF: 0.330 AC: 28424 AN: 86130

European-Finnish (FIN) AF: 0.447 AC: 23865 AN: 53384

Middle Eastern (MID) AF: 0.630 AC: 3624 AN: 5752

European-Non Finnish (NFE) AF: 0.555 AC: 613256 AN: 1104880

Other (OTH) AF: 0.491 AC: 29542 AN: 60140

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

African (AFR) AF: 0.258 AC: 10653 AN: 41324

American (AMR) AF: 0.428 AC: 6517 AN: 15236

Ashkenazi Jewish (ASJ) AF: 0.572 AC: 1982 AN: 3468

East Asian (EAS) AF: 0.115 AC: 595 AN: 5162

South Asian (SAS) AF: 0.314 AC: 1502 AN: 4780

European-Finnish (FIN) AF: 0.450 AC: 4729 AN: 10510

Middle Eastern (MID) AF: 0.595 AC: 175 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 37914 AN: 67842

Other (OTH) AF: 0.512 AC: 1081 AN: 2110

Alfa AF: 0.516 Hom.: 66392

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:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Intellectual developmental disorder 59 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:1

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.31
CADD	Benign	12
DANN	Benign	0.56
PhyloP100		2.0
Mutation Taster		=96/4	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: rs2675671; hg19: chr10-75632760; COSMIC: COSV59480719;