1-33011126-G-A

Position:

• chr1-33011126-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001625.4(AK2):​c.*2055C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0142 in 1,404,948 control chromosomes in the GnomAD database, including 449 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.036 (236 hom., cov: 33)
  • Exomes 𝑓: 0.012 (213 hom.)
• Consequence: AK2 NM_001625.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.176

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.66).
• BP6: Variant 1-33011126-G-A is Benign according to our data. Variant chr1-33011126-G-A is described in ClinVar as [Benign]. Clinvar id is 1246813.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.102 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
AK2	NM_001625.4	c.*2055C>T		3_prime_UTR_variant	6/6	ENST00000672715.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
AK2	ENST00000672715.1	c.*2055C>T		3_prime_UTR_variant	6/6		NM_001625.4	P3
	ENST00000427524.1	n.246-19909G>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0358 AC: 5441 AN: 152102 Hom.: 233 Cov.: 33

Gnomad AFR AF: 0.104

Gnomad AMI AF: 0.114

Gnomad AMR AF: 0.0175

Gnomad ASJ AF: 0.000288

Gnomad EAS AF: 0.000192

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.00113

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.0101

Gnomad OTH AF: 0.0249

GnomAD4 exome AF: 0.0116 AC: 14521 AN: 1252728 Hom.: 213 Cov.: 36 AF XY: 0.0113 AC XY: 6853 AN XY: 608550

Gnomad4 AFR exome AF: 0.105

Gnomad4 AMR exome AF: 0.0119

Gnomad4 ASJ exome AF: 0.000663

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00187

Gnomad4 FIN exome AF: 0.00227

Gnomad4 NFE exome AF: 0.0104

Gnomad4 OTH exome AF: 0.0127

GnomAD4 genome AF: 0.0359 AC: 5466 AN: 152220 Hom.: 236 Cov.: 33 AF XY: 0.0344 AC XY: 2563 AN XY: 74426

Gnomad4 AFR AF: 0.104

Gnomad4 AMR AF: 0.0174

Gnomad4 ASJ AF: 0.000288

Gnomad4 EAS AF: 0.000193

Gnomad4 SAS AF: 0.00270

Gnomad4 FIN AF: 0.00113

Gnomad4 NFE AF: 0.0101

Gnomad4 OTH AF: 0.0246

Alfa AF: 0.0237 Hom.: 18

Bravo AF: 0.0396

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jul 07, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.76

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs79775969; hg19: chr1-33476727;