Genetic Variant AK2:p.Glu9Gln (chr1-33036804-C-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_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. 15/22 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

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.573

Publications

3 publications found

Variant links:

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]

AK2 Gene-Disease associations (from GenCC):

reticular dysgenesis
Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, ClinGen, Orphanet

AK2 links:

ENSG00000236065 (HGNC:58388):

ENSG00000236065 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.12254766).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001625.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AK2	NM_001625.4	MANE Select	c.25G>C	p.Glu9Gln	missense	Exon 1 of 6	NP_001616.1	P54819-1
AK2	NM_001319141.3		c.25G>C	p.Glu9Gln	missense	Exon 1 of 8	NP_001306070.1	F8W1A4
AK2	NM_013411.5		c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	NP_037543.1	P54819-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
AK2	ENST00000672715.1	MANE Select	c.25G>C	p.Glu9Gln	missense	Exon 1 of 6	ENSP00000499935.1	P54819-1
AK2	ENST00000373449.7	TSL:1	c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	ENSP00000362548.2	P54819-2
AK2	ENST00000354858.11	TSL:1	c.25G>C	p.Glu9Gln	missense	Exon 1 of 5	ENSP00000346921.7	A0A5K1VW67

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.089

BayesDel_addAF

Benign

-0.042

BayesDel_noAF

Benign

-0.30

CADD

Benign

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.018

Eigen

Benign

-0.68

Eigen_PC

Benign

-0.77

FATHMM_MKL

Benign

0.76

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.042

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.83

MutationAssessor

Benign

0.60

PhyloP100

0.57

PrimateAI

Uncertain

0.51

PROVEAN

Benign

-0.18

REVEL

Benign

0.17

Sift

Benign

0.28

Sift4G

Benign

0.25

Polyphen

0.81

Vest4

0.26

MutPred

0.14

Loss of glycosylation at P10 (P = 0.0757)

MVP

0.64

MPC

0.29

ClinPred

0.15

GERP RS

0.87

PromoterAI

0.0052

Neutral

(source)

Varity_R

0.17

gMVP

0.67

Mutation Taster

=94/6

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over