1-33021616-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate

The NM_001625.4(AK2):c.307C>A(p.Arg103Arg) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000204 in 1,613,962 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 (★). Synonymous variant affecting the same amino acid position (i.e. R103R) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 31)

Exomes 𝑓: 0.000022 ( 0 hom. )

Consequence

AK2
NM_001625.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 5.25

Publications

6 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), Ambry Genetics, ClinGen, Orphanet, G2P

AK2 links:

ENSG00000236065 (HGNC:58388):

ENSG00000236065 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.29).

BP6

Variant 1-33021616-G-T is Benign according to our data. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr1-33021616-G-T is described in CliVar as Likely_benign. Clinvar id is 665542.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
AK2	NM_001625.4 link	c.307C>A	p.Arg103Arg	synonymous_variant	Exon 3 of 6	ENST00000672715.1	NP_001616.1	P54819-1A0A140VK93

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715.1 link	c.307C>A	p.Arg103Arg	synonymous_variant	Exon 3 of 6		NM_001625.4	ENSP00000499935.1		P54819-1

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.000478

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251378

AF XY:

0.0000147

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000219

AC:

AN:

1461808

Hom.:

Cov.:

AF XY:

0.0000206

AC XY:

AN XY:

727226

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39698

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.0000252

AC:

AN:

1111932

Other (OTH)

AF:

0.0000662

AC:

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74328

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

41434

American (AMR)

AF:

0.00

AC:

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5202

South Asian (SAS)

AF:

0.00

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68024

Other (OTH)

AF:

0.000478

AC:

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000373

Hom.:

Bravo

AF:

0.0000151

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Reticular dysgenesis

Benign:1

Feb 26, 2024

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.29

CADD

Benign

(source)

DANN

Benign

0.84

PhyloP100

5.2

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=47/53

disease causing

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.12

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over