1-33013253-G-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_Strong BP6_Moderate BP7

The NM_001625.4(AK2):c.648C>T(p.Pro216=) 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 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.00013 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: AK2 NM_001625.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.10

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 -7 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-33013253-G-A is Benign according to our data. Variant chr1-33013253-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 1086743.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.1 with no splicing effect.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK2	NM_001625.4	c.648C>T	p.Pro216=	synonymous_variant	6/6	ENST00000672715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK2	ENST00000672715.1	c.648C>T	p.Pro216=	synonymous_variant	6/6		NM_001625.4	P3
	ENST00000427524.1	n.246-17782G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.00 AC: 16 AN: 149186 Hom.: 0 Cov.: 32 FAILED QC

Gnomad AFR AF: 0.000173

Gnomad AMI AF: 0.00111

Gnomad AMR AF: 0.0000673

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000975

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000894

Gnomad OTH AF: 0.00

GnomAD3 exomes AF: 0.0000399 AC: 10 AN: 250850 Hom.: 0 AF XY: 0.0000221 AC XY: 3 AN XY: 135682

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000289

Gnomad ASJ exome AF: 0.0000994

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000705

Gnomad OTH exome AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000130 AC: 190 AN: 1456630 Hom.: 1 Cov.: 34 AF XY: 0.000109 AC XY: 79 AN XY: 724728

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000448

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000233

Gnomad4 FIN exome AF: 0.0000585

Gnomad4 NFE exome AF: 0.000163

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000107 AC: 16 AN: 149304 Hom.: 0 Cov.: 32 AF XY: 0.000165 AC XY: 12 AN XY: 72828

Gnomad4 AFR AF: 0.000173

Gnomad4 AMR AF: 0.0000672

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000975

Gnomad4 NFE AF: 0.0000894

Gnomad4 OTH AF: 0.00

Alfa AF: 0.0606 Hom.: 0

EpiCase AF: 0.000109

EpiControl AF: 0.000178

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Reticular dysgenesis Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Invitae

Oct 05, 2022

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
Cadd	Benign	7.8
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: rs201622956; hg19: chr1-33478854; COSMIC: COSV61468585; COSMIC: COSV61468585;