NM_001625.4:c.*195_*196dupTG

Variant names:

• chr1-33012984-G-GCA
• rs368005323
• NM_001625.4:c.*195_*196dupTG

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001625.4(AK2):​c.*195_*196dupTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,490,574 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (1 hom.)
• Consequence: AK2 NM_001625.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229

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]

ENSG00000236065 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00182 (274/150518) while in subpopulation AFR AF= 0.00221 (91/41110). AF 95% confidence interval is 0.00192. There are 2 homozygotes in gnomad4. There are 113 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK2	NM_001625.4	c.*195_*196dupTG		3_prime_UTR_variant	Exon 6 of 6	ENST00000672715.1	NP_001616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715	c.*195_*196dupTG		3_prime_UTR_variant	Exon 6 of 6		NM_001625.4	ENSP00000499935.1

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 274 AN: 150418 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.000581

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.000839

Gnomad FIN AF: 0.000390

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.000972

GnomAD3 exomes AF: 0.00601 AC: 373 AN: 62018 Hom.: 0 AF XY: 0.00582 AC XY: 192 AN XY: 32998

Gnomad AFR exome AF: 0.00704

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.000423

Gnomad EAS exome AF: 0.00393

Gnomad SAS exome AF: 0.00329

Gnomad FIN exome AF: 0.00317

Gnomad NFE exome AF: 0.00836

Gnomad OTH exome AF: 0.00628

GnomAD4 exome AF: 0.00227 AC: 3039 AN: 1340056 Hom.: 1 Cov.: 29 AF XY: 0.00223 AC XY: 1486 AN XY: 666228

Gnomad4 AFR exome AF: 0.00286

Gnomad4 AMR exome AF: 0.00139

Gnomad4 ASJ exome AF: 0.000209

Gnomad4 EAS exome AF: 0.00188

Gnomad4 SAS exome AF: 0.000891

Gnomad4 FIN exome AF: 0.00146

Gnomad4 NFE exome AF: 0.00250

Gnomad4 OTH exome AF: 0.00208

GnomAD4 genome AF: 0.00182 AC: 274 AN: 150518 Hom.: 2 Cov.: 32 AF XY: 0.00154 AC XY: 113 AN XY: 73518

Gnomad4 AFR AF: 0.00221

Gnomad4 AMR AF: 0.00106

Gnomad4 ASJ AF: 0.000581

Gnomad4 EAS AF: 0.00117

Gnomad4 SAS AF: 0.000840

Gnomad4 FIN AF: 0.000390

Gnomad4 NFE AF: 0.00221

Gnomad4 OTH AF: 0.000962

Bravo AF: 0.00181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs368005323; hg19: chr1-33478585;