10-73853123-T-C

Variant names:

• chr10-73853123-T-C
• rs2250140
• NM_001367534.1:c.275+69A>G

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001367534.1(CAMK2G):​c.275+69A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.504 in 1,455,384 control chromosomes in the GnomAD database, including 194,584 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.47 (17522 hom., cov: 32)
  • Exomes 𝑓: 0.51 (177062 hom.)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.151
• Publications: 11 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: Illumina, ClinGen, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.59).
• BP6: Variant 10-73853123-T-C is Benign according to our data. Variant chr10-73853123-T-C is described in ClinVar as Benign. ClinVar VariationId is 1192576.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.555 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001367534.1. 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
	CAMK2G	NM_001367534.1	MANE Select	c.275+69A>G		intron	N/A	NP_001354463.1	H0Y6G2
	CAMK2G	NM_001320898.2		c.275+69A>G		intron	N/A	NP_001307827.1
	CAMK2G	NM_001367544.1		c.275+69A>G		intron	N/A	NP_001354473.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CAMK2G	ENST00000423381.6	TSL:5 MANE Select	c.275+69A>G		intron	N/A	ENSP00000410298.3	H0Y6G2
	CAMK2G	ENST00000322635.7	TSL:1	c.275+69A>G		intron	N/A	ENSP00000315599.3	Q13555-5
	CAMK2G	ENST00000433289.5	TSL:1	c.80+69A>G		intron	N/A	ENSP00000393784.1	Q8WU40

Frequencies

GnomAD3 genomes AF: 0.466 AC: 70826 AN: 151956 Hom.: 17523 Cov.: 32

Gnomad AFR AF: 0.373

Gnomad AMI AF: 0.529

Gnomad AMR AF: 0.439

Gnomad ASJ AF: 0.571

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.601

Gnomad NFE AF: 0.560

Gnomad OTH AF: 0.533

GnomAD4 exome AF: 0.509 AC: 663133 AN: 1303310 Hom.: 177062 AF XY: 0.506 AC XY: 332659 AN XY: 656902

African (AFR) AF: 0.362 AC: 10942 AN: 30220

American (AMR) AF: 0.317 AC: 14036 AN: 44252

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 14149 AN: 25068

East Asian (EAS) AF: 0.119 AC: 4621 AN: 38906

South Asian (SAS) AF: 0.330 AC: 27387 AN: 82958

European-Finnish (FIN) AF: 0.447 AC: 23796 AN: 53232

Middle Eastern (MID) AF: 0.636 AC: 3476 AN: 5466

European-Non Finnish (NFE) AF: 0.555 AC: 537315 AN: 968094

Other (OTH) AF: 0.497 AC: 27411 AN: 55114

GnomAD4 genome AF: 0.466 AC: 70851 AN: 152074 Hom.: 17522 Cov.: 32 AF XY: 0.459 AC XY: 34111 AN XY: 74336

African (AFR) AF: 0.373 AC: 15464 AN: 41486

American (AMR) AF: 0.438 AC: 6700 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.571 AC: 1980 AN: 3470

East Asian (EAS) AF: 0.115 AC: 593 AN: 5162

South Asian (SAS) AF: 0.317 AC: 1527 AN: 4824

European-Finnish (FIN) AF: 0.451 AC: 4772 AN: 10582

Middle Eastern (MID) AF: 0.609 AC: 179 AN: 294

European-Non Finnish (NFE) AF: 0.560 AC: 38043 AN: 67960

Other (OTH) AF: 0.529 AC: 1112 AN: 2104

Alfa AF: 0.488 Hom.: 2390

Bravo AF: 0.460

Asia WGS AF: 0.207 AC: 719 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Intellectual developmental disorder 59 (1)
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.59
CADD	Benign	15
DANN	Benign	0.86
PhyloP100		0.15
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: rs2250140; hg19: chr10-75612881; COSMIC: COSV59482054; COSMIC: COSV59482054;