rs10914658

Variant names:

• chr1-33065149-G-A
• rs10914658
• ENST00000548559.1:n.189+15050C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The ENST00000548559.1(AK2):​n.189+15050C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0138 in 152,292 control chromosomes in the GnomAD database, including 46 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 0.014 (46 hom., cov: 32)
• Consequence: AK2 ENST00000548559.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.137

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0138 (2105/152292) while in subpopulation AFR AF= 0.0482 (2001/41548). AF 95% confidence interval is 0.0464. There are 46 homozygotes in gnomad4. There are 975 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 46 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000548559.1	n.189+15050C>T		intron_variant	Intron 2 of 4	4

Frequencies

GnomAD3 genomes AF: 0.0138 AC: 2101 AN: 152174 Hom.: 46 Cov.: 32

Gnomad AFR AF: 0.0482

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00478

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.0105

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0138 AC: 2105 AN: 152292 Hom.: 46 Cov.: 32 AF XY: 0.0131 AC XY: 975 AN XY: 74480

Gnomad4 AFR AF: 0.0482

Gnomad4 AMR AF: 0.00477

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000132

Gnomad4 OTH AF: 0.0104

Alfa AF: 0.00510 Hom.: 3

Bravo AF: 0.0161

Asia WGS AF: 0.00433 AC: 15 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	5.8
DANN	Benign	0.35

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs10914658; hg19: chr1-33530750;