chr1-33013263-G-T
Variant summary
Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2
The NM_001625.4(AK2):c.638C>A(p.Ser213Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000421 in 1,613,732 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000044 ( 0 hom. )
Consequence
AK2
NM_001625.4 missense
NM_001625.4 missense
Scores
2
8
8
Clinical Significance
Conservation
PhyloP100: 8.04
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 Uncertain_significance. Variant got 2 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
AK2 | NM_001625.4 | c.638C>A | p.Ser213Tyr | missense_variant | 6/6 | ENST00000672715.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
AK2 | ENST00000672715.1 | c.638C>A | p.Ser213Tyr | missense_variant | 6/6 | NM_001625.4 | P3 | ||
ENST00000427524.1 | n.246-17772G>T | intron_variant, non_coding_transcript_variant | 2 |
Frequencies
GnomAD3 genomes ? AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000159 AC: 4AN: 251452Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135902
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GnomAD4 exome AF: 0.0000445 AC: 65AN: 1461542Hom.: 0 Cov.: 34 AF XY: 0.0000523 AC XY: 38AN XY: 727112
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GnomAD4 genome ? AF: 0.0000197 AC: 3AN: 152190Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74352
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Reticular dysgenesis Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 20, 2021 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with AK2-related disease. This variant is present in population databases (rs139238739, ExAC 0.003%). This sequence change replaces serine with tyrosine at codon 213 of the AK2 protein (p.Ser213Tyr). The serine residue is moderately conserved and there is a large physicochemical difference between serine and tyrosine. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
D
BayesDel_noAF
Uncertain
Cadd
Uncertain
Dann
Uncertain
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Benign
T;T;T;T
M_CAP
Benign
D
MetaRNN
Uncertain
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;.;L
MutationTaster
Benign
D;D;D;D;D
PrimateAI
Benign
T
PROVEAN
Pathogenic
D;D;D;D
REVEL
Uncertain
Sift
Benign
D;D;D;D
Sift4G
Uncertain
T;T;T;T
Polyphen
B;B;.;B
Vest4
MVP
MPC
0.24
ClinPred
D
GERP RS
Varity_R
gMVP
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