1-33012984-GCACACACA-GCACACACACACA

Variant names:

• chr1-33012984-G-GCACA
• rs368005323
• NM_001625.4:c.*193_*196dupTGTG

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2 BS1

The NM_001625.4(AK2):​c.*193_*196dupTGTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000293 in 1,501,196 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.000093 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000022 (0 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 Likely_benign. Variant got -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000093 (14/150538) while in subpopulation AFR AF= 0.000316 (13/41114). AF 95% confidence interval is 0.000187. There are 0 homozygotes in gnomad4. There are 9 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK2	NM_001625.4	c.*193_*196dupTGTG		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.*193_*196dupTGTG		3_prime_UTR_variant	Exon 6 of 6		NM_001625.4	ENSP00000499935.1

Frequencies

GnomAD3 genomes AF: 0.0000931 AC: 14 AN: 150438 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000317

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.000486

GnomAD3 exomes AF: 0.0000806 AC: 5 AN: 62018 Hom.: 0 AF XY: 0.0000909 AC XY: 3 AN XY: 32998

Gnomad AFR exome AF: 0.00101

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000143

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000222 AC: 30 AN: 1350658 Hom.: 0 Cov.: 29 AF XY: 0.0000283 AC XY: 19 AN XY: 671336

Gnomad4 AFR exome AF: 0.000330

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000250

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000172

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000930 AC: 14 AN: 150538 Hom.: 0 Cov.: 32 AF XY: 0.000122 AC XY: 9 AN XY: 73528

Gnomad4 AFR AF: 0.000316

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.000481

Bravo AF: 0.000110

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;