chr5-150223261-C-T

Variant names:

• chr5-150223261-C-T
• rs2241695
• NM_015981.4:c.1238-44G>A

Variant summary

Our verdict is Benign. The variant received -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_015981.4(CAMK2A):​c.1238-44G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.543 in 1,476,122 control chromosomes in the GnomAD database, including 222,905 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.47 (18552 hom., cov: 31)
  • Exomes 𝑓: 0.55 (204353 hom.)
• Consequence: CAMK2A NM_015981.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -0.527
• Publications: 24 publications found

Genes affected

CAMK2A (HGNC:1460): (calcium/calmodulin dependent protein kinase II alpha) The product of this gene belongs to the serine/threonine protein kinases family, and to the Ca(2+)/calmodulin-dependent protein kinases subfamily. Calcium signaling is crucial for several aspects of plasticity at glutamatergic synapses. This calcium calmodulin-dependent protein kinase is composed of four different chains: alpha, beta, gamma, and delta. The alpha chain encoded by this gene is required for hippocampal long-term potentiation (LTP) and spatial learning. In addition to its calcium-calmodulin (CaM)-dependent activity, this protein can undergo autophosphorylation, resulting in CaM-independent activity. Several transcript variants encoding distinct isoforms have been identified for this gene. [provided by RefSeq, Jun 2018]

CAMK2A Gene-Disease associations (from GenCC):

• intellectual disability, autosomal dominant 53

  Inheritance: AD Classification: STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• autosomal dominant non-syndromic intellectual disability

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• intellectual disability, autosomal recessive 63

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.74).
• BP6: Variant 5-150223261-C-T is Benign according to our data. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-150223261-C-T is described in CliVar as Benign. Clinvar id is 1192690.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.608 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2A	NM_015981.4	c.1238-44G>A		intron_variant	Intron 17 of 18	ENST00000671881.1	NP_057065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2A	ENST00000671881.1	c.1238-44G>A		intron_variant	Intron 17 of 18		NM_015981.4	ENSP00000500386.1

Frequencies

GnomAD3 genomes AF: 0.469 AC: 71264 AN: 151810 Hom.: 18547 Cov.: 31

Gnomad AFR AF: 0.223

Gnomad AMI AF: 0.610

Gnomad AMR AF: 0.517

Gnomad ASJ AF: 0.608

Gnomad EAS AF: 0.626

Gnomad SAS AF: 0.495

Gnomad FIN AF: 0.614

Gnomad MID AF: 0.557

Gnomad NFE AF: 0.562

Gnomad OTH AF: 0.501

GnomAD2 exomes AF: 0.537 AC: 117021 AN: 217732 AF XY: 0.543

Gnomad AFR exome AF: 0.225

Gnomad AMR exome AF: 0.483

Gnomad ASJ exome AF: 0.624

Gnomad EAS exome AF: 0.617

Gnomad FIN exome AF: 0.628

Gnomad NFE exome AF: 0.572

Gnomad OTH exome AF: 0.563

GnomAD4 exome AF: 0.551 AC: 729794 AN: 1324194 Hom.: 204353 Cov.: 19 AF XY: 0.551 AC XY: 365227 AN XY: 662766

African (AFR) AF: 0.213 AC: 6641 AN: 31126

American (AMR) AF: 0.482 AC: 20355 AN: 42244

Ashkenazi Jewish (ASJ) AF: 0.616 AC: 15351 AN: 24930

East Asian (EAS) AF: 0.646 AC: 24952 AN: 38606

South Asian (SAS) AF: 0.492 AC: 40518 AN: 82324

European-Finnish (FIN) AF: 0.617 AC: 28682 AN: 46502

Middle Eastern (MID) AF: 0.529 AC: 2846 AN: 5384

European-Non Finnish (NFE) AF: 0.562 AC: 559950 AN: 997198

Other (OTH) AF: 0.546 AC: 30499 AN: 55880

GnomAD4 genome AF: 0.469 AC: 71282 AN: 151928 Hom.: 18552 Cov.: 31 AF XY: 0.474 AC XY: 35232 AN XY: 74254

African (AFR) AF: 0.223 AC: 9235 AN: 41474

American (AMR) AF: 0.517 AC: 7881 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.608 AC: 2109 AN: 3468

East Asian (EAS) AF: 0.626 AC: 3216 AN: 5140

South Asian (SAS) AF: 0.496 AC: 2385 AN: 4804

European-Finnish (FIN) AF: 0.614 AC: 6492 AN: 10572

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.562 AC: 38178 AN: 67904

Other (OTH) AF: 0.502 AC: 1059 AN: 2108

Alfa AF: 0.543 Hom.: 42071

Bravo AF: 0.452

Asia WGS AF: 0.537 AC: 1867 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, single submitter

Submissions by phenotype

Intellectual disability, autosomal recessive 63 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Intellectual disability, autosomal dominant 53 Benign:1

Jul 14, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.74
CADD	Benign	5.8
DANN	Benign	0.72
PhyloP100		-0.53
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: rs2241695; hg19: chr5-149602824; COSMIC: COSV62245604; COSMIC: COSV62245604;