rs746330303

chr1-33013271-G-Achr1-33013271-G-C

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Moderate BP6_Very_Strong BP7

The NM_001625.4(AK2):c.630C>T(p.Ile210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

• Frequency:
  • Genomes: 𝑓 0.00031 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000037 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: AK2 NM_001625.4 synonymous
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.138

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]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 1-33013271-G-A is Benign according to our data. Variant chr1-33013271-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 529735.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-33013271-G-A is described in Lovd as [Benign].
• BP7: Synonymous conserved (PhyloP=0.138 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK2	NM_001625.4	c.630C>T	p.Ile210=	synonymous_variant	6/6	ENST00000672715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK2	ENST00000672715.1	c.630C>T	p.Ile210=	synonymous_variant	6/6		NM_001625.4	P3
	ENST00000427524.1	n.246-17764G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 45 AN: 144128 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000485

Gnomad AMI AF: 0.00114

Gnomad AMR AF: 0.000139

Gnomad ASJ AF: 0.000300

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000220

Gnomad FIN AF: 0.000408

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000247

Gnomad OTH AF: 0.000512

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000365 AC: 52 AN: 1423174 Hom.: 0 Cov.: 34 AF XY: 0.0000339 AC XY: 24 AN XY: 708852

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000255

Gnomad4 SAS exome AF: 0.0000118

Gnomad4 FIN exome AF: 0.000628

Gnomad4 NFE exome AF: 0.0000157

Gnomad4 OTH exome AF: 0.0000676

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000312 AC: 45 AN: 144236 Hom.: 0 Cov.: 32 AF XY: 0.000371 AC XY: 26 AN XY: 70046

Gnomad4 AFR AF: 0.000483

Gnomad4 AMR AF: 0.000139

Gnomad4 ASJ AF: 0.000300

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000220

Gnomad4 FIN AF: 0.000408

Gnomad4 NFE AF: 0.000247

Gnomad4 OTH AF: 0.000507

Alfa AF: 0.00154 Hom.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Reticular dysgenesis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Dec 18, 2023

- -

AK2-related condition Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Sep 11, 2021

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
Cadd	Benign	9.3
Dann	Benign	0.86

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: rs746330303; hg19: chr1-33478872; COSMIC: COSV61468263; COSMIC: COSV61468263;