rs79775969

Variant names:

• chr1-33011126-G-A
• rs79775969
• NM_001625.4:c.*2055C>T

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 0 publications found

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

ENSG00000236065 (HGNC:58388):

ACMG classification

Our verdict: Benign. The variant received -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 VariationId 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.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK2	NM_001625.4	MANE Select	c.*2055C>T		3_prime_UTR	Exon 6 of 6	NP_001616.1	P54819-1
	AK2	NM_001319140.2		c.*2055C>T		3_prime_UTR	Exon 7 of 7	NP_001306069.1	P54819-6
	AK2	NM_001319143.2		c.*2278C>T		3_prime_UTR	Exon 5 of 5	NP_001306072.1	G3V213

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK2	ENST00000672715.1	MANE Select	c.*2055C>T		3_prime_UTR	Exon 6 of 6	ENSP00000499935.1	P54819-1
	AK2	ENST00000354858.11	TSL:1	c.*2055C>T		3_prime_UTR	Exon 5 of 5	ENSP00000346921.7	A0A5K1VW67
	AK2	ENST00000373449.7	TSL:1	c.695-293C>T		intron	N/A	ENSP00000362548.2	P54819-2

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

African (AFR) AF: 0.105 AC: 2896 AN: 27650

American (AMR) AF: 0.0119 AC: 248 AN: 20840

Ashkenazi Jewish (ASJ) AF: 0.000663 AC: 12 AN: 18112

East Asian (EAS) AF: 0.00 AC: 0 AN: 30978

South Asian (SAS) AF: 0.00187 AC: 117 AN: 62694

European-Finnish (FIN) AF: 0.00227 AC: 58 AN: 25598

Middle Eastern (MID) AF: 0.0165 AC: 56 AN: 3392

European-Non Finnish (NFE) AF: 0.0104 AC: 10481 AN: 1012186

Other (OTH) AF: 0.0127 AC: 653 AN: 51278

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

African (AFR) AF: 0.104 AC: 4326 AN: 41508

American (AMR) AF: 0.0174 AC: 266 AN: 15280

Ashkenazi Jewish (ASJ) AF: 0.000288 AC: 1 AN: 3470

East Asian (EAS) AF: 0.000193 AC: 1 AN: 5184

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4816

European-Finnish (FIN) AF: 0.00113 AC: 12 AN: 10610

Middle Eastern (MID) AF: 0.0238 AC: 7 AN: 294

European-Non Finnish (NFE) AF: 0.0101 AC: 684 AN: 68032

Other (OTH) AF: 0.0246 AC: 52 AN: 2114

Alfa AF: 0.0237 Hom.: 18

Bravo AF: 0.0396

Asia WGS AF: 0.00779 AC: 27 AN: 3478

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.66
CADD	Benign	8.4
DANN	Benign	0.76
PhyloP100		0.18
Mutation Taster		=98/2	polymorphism (auto)

Splicing

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

Other links and lift over

dbSNP: rs79775969; hg19: chr1-33476727;