NM_001625.4:c.660C>A

Variant names:

• chr1-33013241-G-T
• rs566166581
• NM_001625.4:c.660C>A

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_001625.4(AK2):​c.660C>A​(p.Phe220Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F220Y) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AK2 NM_001625.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.798

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 Uncertain_significance. Variant got 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.28427988).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK2	NM_001625.4	c.660C>A	p.Phe220Leu	missense_variant	Exon 6 of 6	ENST00000672715.1	NP_001616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715.1	c.660C>A	p.Phe220Leu	missense_variant	Exon 6 of 6		NM_001625.4	ENSP00000499935.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.96
BayesDel_addAF	Benign	-0.00062	T
BayesDel_noAF	Benign	-0.24
CADD	Benign	18
DANN	Uncertain	0.98
DEOGEN2	Benign	0.11	.;T;T;T
Eigen	Benign	-0.64
Eigen_PC	Benign	-0.57
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.89	D;D;D;D
M_CAP	Benign	0.047	D
MetaRNN	Benign	0.28	T;T;T;T
MetaSVM	Benign	-0.81	T
MutationAssessor	Benign	1.8	L;.;.;L
PrimateAI	Uncertain	0.72	T
PROVEAN	Pathogenic	-4.5	D;D;D;D
REVEL	Uncertain	0.29
Sift	Benign	0.044	D;D;D;T
Sift4G	Benign	0.19	T;T;T;T
Polyphen		0.27	B;B;.;B
Vest4		0.35
MutPred		0.49		Loss of catalytic residue at F220 (P = 0.0415);.;Loss of catalytic residue at F220 (P = 0.0415);Loss of catalytic residue at F220 (P = 0.0415);
MVP		0.51
MPC		0.22
ClinPred		0.93	D
GERP RS		-0.89
Varity_R		0.63
gMVP		0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs566166581; hg19: chr1-33478842;