chr1-33036804-C-G

Position:

• chr1-33036804-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001625.4(AK2):​c.25G>C​(p.Glu9Gln) 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. 14/21 in silico tools predict 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. E9K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AK2 NM_001625.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12254766).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK2	NM_001625.4	c.25G>C	p.Glu9Gln	missense_variant	1/6	ENST00000672715.1	NP_001616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715.1	c.25G>C	p.Glu9Gln	missense_variant	1/6		NM_001625.4	ENSP00000499935.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	.;.;T;T;.;T;.;T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.90	D;D;D;D;.;D;D;D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.12	T;T;T;T;T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.60	.;N;.;.;.;N;.;.
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.18	.;N;N;N;N;N;N;.
REVEL	Benign	0.17
Sift	Benign	0.28	.;T;T;T;T;T;T;.
Sift4G	Benign	0.25	T;T;T;T;T;T;T;T
Polyphen		0.81, 0.87, 0.82	.;P;P;.;.;P;.;.
Vest4		0.26
MutPred		0.14		Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);Loss of glycosylation at P10 (P = 0.0757);
MVP		0.64
MPC		0.29
ClinPred		0.15	T
GERP RS		0.87
Varity_R		0.17
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		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: rs267606647; hg19: chr1-33502405;