chr1-33009825-C-T

Position:

• chr1-33009825-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001625.4(AK2):​c.*3356G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.261 in 454,208 control chromosomes in the GnomAD database, including 17,541 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.22 (4490 hom., cov: 32)
  • Exomes 𝑓: 0.28 (13051 hom.)
• Consequence: AK2 NM_001625.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.36

Genes affected

AK2 (HGNC:362): (adenylate kinase 2) Adenylate kinases are involved in regulating the adenine nucleotide composition within a cell by catalyzing the reversible transfer of phosphate groups among adenine nucleotides. Three isozymes of adenylate kinase, namely 1, 2, and 3, have been identified in vertebrates; this gene encodes isozyme 2. Expression of these isozymes is tissue-specific and developmentally regulated. Isozyme 2 is localized in the mitochondrial intermembrane space and may play a role in apoptosis. Mutations in this gene are the cause of reticular dysgenesis. Alternate splicing results in multiple transcript variants. Pseudogenes of this gene are found on chromosomes 1 and 2.[provided by RefSeq, Nov 2010]

AK2 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.348 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK2	NM_001625.4	c.*3356G>A		3_prime_UTR_variant	6/6	ENST00000672715.1	NP_001616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715	c.*3356G>A		3_prime_UTR_variant	6/6		NM_001625.4	ENSP00000499935.1

Frequencies

GnomAD3 genomes AF: 0.218 AC: 33185 AN: 151912 Hom.: 4491 Cov.: 32

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.117

Gnomad AMR AF: 0.356

Gnomad ASJ AF: 0.194

Gnomad EAS AF: 0.269

Gnomad SAS AF: 0.305

Gnomad FIN AF: 0.277

Gnomad MID AF: 0.228

Gnomad NFE AF: 0.268

Gnomad OTH AF: 0.223

GnomAD3 exomes AF: 0.292 AC: 39883 AN: 136480 Hom.: 6553 AF XY: 0.289 AC XY: 21380 AN XY: 74088

Gnomad AFR exome AF: 0.0552

Gnomad AMR exome AF: 0.445

Gnomad ASJ exome AF: 0.199

Gnomad EAS exome AF: 0.280

Gnomad SAS exome AF: 0.316

Gnomad FIN exome AF: 0.272

Gnomad NFE exome AF: 0.263

Gnomad OTH exome AF: 0.260

GnomAD4 exome AF: 0.283 AC: 85455 AN: 302178 Hom.: 13051 Cov.: 0 AF XY: 0.283 AC XY: 48826 AN XY: 172232

Gnomad4 AFR exome AF: 0.0578

Gnomad4 AMR exome AF: 0.445

Gnomad4 ASJ exome AF: 0.197

Gnomad4 EAS exome AF: 0.267

Gnomad4 SAS exome AF: 0.315

Gnomad4 FIN exome AF: 0.271

Gnomad4 NFE exome AF: 0.266

Gnomad4 OTH exome AF: 0.244

GnomAD4 genome AF: 0.218 AC: 33182 AN: 152030 Hom.: 4490 Cov.: 32 AF XY: 0.225 AC XY: 16698 AN XY: 74302

Gnomad4 AFR AF: 0.0585

Gnomad4 AMR AF: 0.356

Gnomad4 ASJ AF: 0.194

Gnomad4 EAS AF: 0.270

Gnomad4 SAS AF: 0.305

Gnomad4 FIN AF: 0.277

Gnomad4 NFE AF: 0.268

Gnomad4 OTH AF: 0.221

Alfa AF: 0.248 Hom.: 5049

Bravo AF: 0.216

Asia WGS AF: 0.211 AC: 732 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	0.15
DANN	Benign	0.57
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.1

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs998664; hg19: chr1-33475426;