1-33010544-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001625.4(AK2):c.*2637A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00543 in 794,688 control chromosomes in the GnomAD database, including 121 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0034 (0 hom., cov: 45)
  • Exomes 𝑓: 0.0059 (121 hom.)
• Consequence: AK2 NM_001625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.59

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.78).
• BP6: Variant 1-33010544-T-C is Benign according to our data. Variant chr1-33010544-T-C is described in ClinVar as [Benign]. Clinvar id is 1262330.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.0806 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK2	NM_001625.4	c.*2637A>G		3_prime_UTR_variant	6/6	ENST00000672715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK2	ENST00000672715.1	c.*2637A>G		3_prime_UTR_variant	6/6		NM_001625.4	P3
	ENST00000427524.1	n.246-20491T>C		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00340 AC: 517 AN: 152272 Hom.: 0 Cov.: 45

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000262

Gnomad ASJ AF: 0.00317

Gnomad EAS AF: 0.0870

Gnomad SAS AF: 0.00579

Gnomad FIN AF: 0.0000941

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000220

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00850 AC: 1126 AN: 132466 Hom.: 20 AF XY: 0.00816 AC XY: 590 AN XY: 72302

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000820

Gnomad ASJ exome AF: 0.00246

Gnomad EAS exome AF: 0.0922

Gnomad SAS exome AF: 0.00317

Gnomad FIN exome AF: 0.000183

Gnomad NFE exome AF: 0.000256

Gnomad OTH exome AF: 0.00542

GnomAD4 exome AF: 0.00592 AC: 3801 AN: 642298 Hom.: 121 Cov.: 8 AF XY: 0.00590 AC XY: 2015 AN XY: 341500

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000870

Gnomad4 ASJ exome AF: 0.00296

Gnomad4 EAS exome AF: 0.104

Gnomad4 SAS exome AF: 0.00379

Gnomad4 FIN exome AF: 0.000281

Gnomad4 NFE exome AF: 0.000277

Gnomad4 OTH exome AF: 0.00368

GnomAD4 genome AF: 0.00338 AC: 515 AN: 152390 Hom.: 0 Cov.: 45 AF XY: 0.00407 AC XY: 303 AN XY: 74526

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.000261

Gnomad4 ASJ AF: 0.00317

Gnomad4 EAS AF: 0.0872

Gnomad4 SAS AF: 0.00538

Gnomad4 FIN AF: 0.0000941

Gnomad4 NFE AF: 0.000220

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00160 Hom.: 0

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 18, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.78
Cadd	Benign	10
Dann	Benign	0.81
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		0.97

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs147782001; hg19: chr1-33476145; COSMIC: COSV61467880; COSMIC: COSV61467880;