1-33012984-G-GCA

Variant names:

• chr1-33012984-G-GCA
• rs368005323
• NM_001625.4:c.*195_*196dupTG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BS1 BS2

The NM_001625.4(AK2):​c.*195_*196dupTG variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00222 in 1,490,574 control chromosomes in the GnomAD database, including 3 homozygotes. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0018 (2 hom., cov: 32)
  • Exomes 𝑓: 0.0023 (1 hom.)
• Consequence: AK2 NM_001625.4 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.229
• Publications: 1 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: ClinGen, Orphanet, Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)

ENSG00000236065 (HGNC:58388):

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00182 (274/150518) while in subpopulation AFR AF = 0.00221 (91/41110). AF 95% confidence interval is 0.00192. There are 2 homozygotes in GnomAd4. There are 113 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 2 AR gene

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.*195_*196dupTG		3_prime_UTR	Exon 6 of 6	NP_001616.1	P54819-1
	AK2	NM_001319140.2		c.*195_*196dupTG		3_prime_UTR	Exon 7 of 7	NP_001306069.1	P54819-6
	AK2	NM_001319143.2		c.*418_*419dupTG		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.*195_*196dupTG		3_prime_UTR	Exon 6 of 6	ENSP00000499935.1	P54819-1
	AK2	ENST00000354858.11	TSL:1	c.*195_*196dupTG		3_prime_UTR	Exon 5 of 5	ENSP00000346921.7	A0A5K1VW67
	AK2	ENST00000373449.7	TSL:1	c.694+221_694+222dupTG		intron	N/A	ENSP00000362548.2	P54819-2

Frequencies

GnomAD3 genomes AF: 0.00182 AC: 274 AN: 150418 Hom.: 2 Cov.: 32

Gnomad AFR AF: 0.00222

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00106

Gnomad ASJ AF: 0.000581

Gnomad EAS AF: 0.00117

Gnomad SAS AF: 0.000839

Gnomad FIN AF: 0.000390

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00221

Gnomad OTH AF: 0.000972

GnomAD2 exomes AF: 0.00601 AC: 373 AN: 62018 AF XY: 0.00582

Gnomad AFR exome AF: 0.00704

Gnomad AMR exome AF: 0.00369

Gnomad ASJ exome AF: 0.000423

Gnomad EAS exome AF: 0.00393

Gnomad FIN exome AF: 0.00317

Gnomad NFE exome AF: 0.00836

Gnomad OTH exome AF: 0.00628

GnomAD4 exome AF: 0.00227 AC: 3039 AN: 1340056 Hom.: 1 Cov.: 29 AF XY: 0.00223 AC XY: 1486 AN XY: 666228

African (AFR) AF: 0.00286 AC: 86 AN: 30072

American (AMR) AF: 0.00139 AC: 56 AN: 40418

Ashkenazi Jewish (ASJ) AF: 0.000209 AC: 5 AN: 23884

East Asian (EAS) AF: 0.00188 AC: 67 AN: 35558

South Asian (SAS) AF: 0.000891 AC: 71 AN: 79648

European-Finnish (FIN) AF: 0.00146 AC: 50 AN: 34246

Middle Eastern (MID) AF: 0.000762 AC: 4 AN: 5252

European-Non Finnish (NFE) AF: 0.00250 AC: 2585 AN: 1035702

Other (OTH) AF: 0.00208 AC: 115 AN: 55276

GnomAD4 genome AF: 0.00182 AC: 274 AN: 150518 Hom.: 2 Cov.: 32 AF XY: 0.00154 AC XY: 113 AN XY: 73518

African (AFR) AF: 0.00221 AC: 91 AN: 41110

American (AMR) AF: 0.00106 AC: 16 AN: 15120

Ashkenazi Jewish (ASJ) AF: 0.000581 AC: 2 AN: 3440

East Asian (EAS) AF: 0.00117 AC: 6 AN: 5134

South Asian (SAS) AF: 0.000840 AC: 4 AN: 4764

European-Finnish (FIN) AF: 0.000390 AC: 4 AN: 10250

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.00221 AC: 149 AN: 67420

Other (OTH) AF: 0.000962 AC: 2 AN: 2080

Alfa AF: 0.00131 Hom.: 0

Bravo AF: 0.00181

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		-0.23
Mutation Taster		=100/0	polymorphism

Splicing

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

Other links and lift over

dbSNP: rs368005323; hg19: chr1-33478585;