chr5-150222800-T-A

Variant names:

• chr5-150222800-T-A
• rs17712679
• NM_015981.4:c.1467-87A>T

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.1467-87A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.346 in 1,542,084 control chromosomes in the GnomAD database, including 93,919 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.35 (9282 hom., cov: 32)
  • Exomes 𝑓: 0.35 (84637 hom.)
• Consequence: CAMK2A NM_015981.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:2
• Conservation: PhyloP100: -2.99

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]

SLC6A7 (HGNC:11054): (solute carrier family 6 member 7) This gene is a member of the gamma-aminobutyric acid (GABA) neurotransmitter gene family and encodes a high-affinity mammalian brain L-proline transporter protein. This transporter protein differs from other sodium-dependent plasma membrane carriers by its pharmacological specificity, kinetic properties, and ionic requirements. [provided by RefSeq, Jul 2008]

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.93).
• BP6: Variant 5-150222800-T-A is Benign according to our data. Variant chr5-150222800-T-A is described in ClinVar as [Benign]. Clinvar id is 1192688.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.383 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CAMK2A	NM_015981.4	c.1467-87A>T		intron_variant	Intron 18 of 18	ENST00000671881.1	NP_057065.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CAMK2A	ENST00000671881.1	c.1467-87A>T		intron_variant	Intron 18 of 18		NM_015981.4	ENSP00000500386.1

Frequencies

GnomAD3 genomes AF: 0.348 AC: 52792 AN: 151882 Hom.: 9280 Cov.: 32

Gnomad AFR AF: 0.361

Gnomad AMI AF: 0.249

Gnomad AMR AF: 0.391

Gnomad ASJ AF: 0.271

Gnomad EAS AF: 0.168

Gnomad SAS AF: 0.302

Gnomad FIN AF: 0.317

Gnomad MID AF: 0.358

Gnomad NFE AF: 0.357

Gnomad OTH AF: 0.347

GnomAD4 exome AF: 0.346 AC: 480994 AN: 1390082 Hom.: 84637 Cov.: 23 AF XY: 0.344 AC XY: 239521 AN XY: 695330

Gnomad4 AFR exome AF: 0.354 AC: 11340 AN: 32022

Gnomad4 AMR exome AF: 0.462 AC: 20283 AN: 43948

Gnomad4 ASJ exome AF: 0.266 AC: 6831 AN: 25656

Gnomad4 EAS exome AF: 0.166 AC: 6503 AN: 39270

Gnomad4 SAS exome AF: 0.321 AC: 27136 AN: 84448

Gnomad4 FIN exome AF: 0.311 AC: 16525 AN: 53082

Gnomad4 NFE exome AF: 0.354 AC: 371405 AN: 1049146

Gnomad4 Remaining exome AF: 0.333 AC: 19302 AN: 58010

GnomAD4 genome AF: 0.347 AC: 52813 AN: 152002 Hom.: 9282 Cov.: 32 AF XY: 0.345 AC XY: 25615 AN XY: 74294

Gnomad4 AFR AF: 0.361 AC: 0.360618 AN: 0.360618

Gnomad4 AMR AF: 0.391 AC: 0.390872 AN: 0.390872

Gnomad4 ASJ AF: 0.271 AC: 0.27147 AN: 0.27147

Gnomad4 EAS AF: 0.168 AC: 0.168284 AN: 0.168284

Gnomad4 SAS AF: 0.301 AC: 0.301495 AN: 0.301495

Gnomad4 FIN AF: 0.317 AC: 0.317486 AN: 0.317486

Gnomad4 NFE AF: 0.357 AC: 0.356583 AN: 0.356583

Gnomad4 OTH AF: 0.342 AC: 0.341706 AN: 0.341706

Alfa AF: 0.219 Hom.: 489

Bravo AF: 0.353

Asia WGS AF: 0.221 AC: 772 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	-0.93
CADD	Benign	0.089
DANN	Benign	0.61
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

Publications

LitVar

Other links and lift over

dbSNP: rs17712679; hg19: chr5-149602363; COSMIC: COSV62248375; COSMIC: COSV62248375;