rs138151595
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Variant summary
Our verdict is Benign. Variant got -14 ACMG points: 2P and 16B. PM2BP4_StrongBP6_Very_StrongBS1
The NM_001625.4(AK2):c.603C>T(p.Tyr201=) variant causes a synonymous change. The variant allele was found at a frequency of 0.000353 in 1,614,170 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00033 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00036 ( 0 hom. )
Consequence
AK2
NM_001625.4 synonymous
NM_001625.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 3.67
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -14 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.54).
BP6
Variant 1-33013298-G-A is Benign according to our data. Variant chr1-33013298-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529738.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-33013298-G-A is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000328 (50/152304) while in subpopulation NFE AF= 0.000647 (44/68040). AF 95% confidence interval is 0.000494. There are 0 homozygotes in gnomad4. There are 18 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AK2 | NM_001625.4 | c.603C>T | p.Tyr201= | synonymous_variant | 6/6 | ENST00000672715.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AK2 | ENST00000672715.1 | c.603C>T | p.Tyr201= | synonymous_variant | 6/6 | NM_001625.4 | P3 | ||
ENST00000427524.1 | n.246-17737G>A | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes AF: 0.000329 AC: 50AN: 152186Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000270 AC: 68AN: 251456Hom.: 0 AF XY: 0.000250 AC XY: 34AN XY: 135906
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GnomAD4 exome AF: 0.000355 AC: 519AN: 1461866Hom.: 0 Cov.: 35 AF XY: 0.000391 AC XY: 284AN XY: 727234
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GnomAD4 genome AF: 0.000328 AC: 50AN: 152304Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74470
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ClinVar
Significance: Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Reticular dysgenesis Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Dec 11, 2023 | - - |
AK2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 18, 2023 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Aug 01, 2023 | AK2: BP4, BP7 - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at