NM_001367534.1:c.161-110A>G

Variant names:

• chr10-73860999-T-C
• rs2664282
• NM_001367534.1:c.161-110A>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.161-110A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.471 in 771,000 control chromosomes in the GnomAD database, including 93,655 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.43 (15902 hom., cov: 33)
  • Exomes 𝑓: 0.48 (77753 hom.)
• Consequence: CAMK2G NM_001367534.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.18
• Publications: 14 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=-0.84).
• BP6: Variant 10-73860999-T-C is Benign according to our data. Variant chr10-73860999-T-C is described in ClinVar as Benign. ClinVar VariationId is 1192577.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.161-110A>G		intron	N/A	NP_001354463.1	H0Y6G2
	CAMK2G	NM_001320898.2		c.161-110A>G		intron	N/A	NP_001307827.1
	CAMK2G	NM_001367544.1		c.161-110A>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.161-110A>G		intron	N/A	ENSP00000410298.3	H0Y6G2
	CAMK2G	ENST00000322635.7	TSL:1	c.161-110A>G		intron	N/A	ENSP00000315599.3	Q13555-5
	CAMK2G	ENST00000394762.7	TSL:1	c.-593-110A>G		intron	N/A	ENSP00000378243.4	A0A804CJ50

Frequencies

GnomAD3 genomes AF: 0.434 AC: 65966 AN: 152008 Hom.: 15904 Cov.: 33

Gnomad AFR AF: 0.260

Gnomad AMI AF: 0.524

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.569

Gnomad EAS AF: 0.115

Gnomad SAS AF: 0.315

Gnomad FIN AF: 0.451

Gnomad MID AF: 0.592

Gnomad NFE AF: 0.559

Gnomad OTH AF: 0.518

GnomAD4 exome AF: 0.480 AC: 297214 AN: 618874 Hom.: 77753 AF XY: 0.478 AC XY: 157605 AN XY: 329974

African (AFR) AF: 0.259 AC: 4255 AN: 16440

American (AMR) AF: 0.332 AC: 10878 AN: 32806

Ashkenazi Jewish (ASJ) AF: 0.564 AC: 10474 AN: 18582

East Asian (EAS) AF: 0.120 AC: 4196 AN: 35086

South Asian (SAS) AF: 0.332 AC: 21193 AN: 63766

European-Finnish (FIN) AF: 0.448 AC: 22248 AN: 49666

Middle Eastern (MID) AF: 0.635 AC: 2529 AN: 3982

European-Non Finnish (NFE) AF: 0.561 AC: 205763 AN: 366632

Other (OTH) AF: 0.491 AC: 15678 AN: 31914

GnomAD4 genome AF: 0.434 AC: 65978 AN: 152126 Hom.: 15902 Cov.: 33 AF XY: 0.428 AC XY: 31835 AN XY: 74364

African (AFR) AF: 0.260 AC: 10796 AN: 41502

American (AMR) AF: 0.428 AC: 6551 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.569 AC: 1975 AN: 3470

East Asian (EAS) AF: 0.115 AC: 597 AN: 5170

South Asian (SAS) AF: 0.316 AC: 1524 AN: 4818

European-Finnish (FIN) AF: 0.451 AC: 4774 AN: 10584

Middle Eastern (MID) AF: 0.599 AC: 176 AN: 294

European-Non Finnish (NFE) AF: 0.559 AC: 38024 AN: 67972

Other (OTH) AF: 0.514 AC: 1084 AN: 2110

Alfa AF: 0.529 Hom.: 27427

Bravo AF: 0.424

Asia WGS AF: 0.205 AC: 712 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	-0.84
CADD	Benign	15
DANN	Benign	0.74
PhyloP100		1.2
PromoterAI		0.031	Neutral
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs2664282; hg19: chr10-75620757; COSMIC: COSV59486541; COSMIC: COSV59486541;