1-33036804-C-G

Variant names:

• chr1-33036804-C-G
• rs267606647
• NM_001625.4:c.25G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001625.4(AK2):​c.25G>C​(p.Glu9Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E9K) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: AK2 NM_001625.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.573
• Publications: 3 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12254766).

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.25G>C	p.Glu9Gln	missense	Exon 1 of 6	NP_001616.1	P54819-1
	AK2	NM_001319141.3		c.25G>C	p.Glu9Gln	missense	Exon 1 of 8	NP_001306070.1	F8W1A4
	AK2	NM_013411.5		c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	NP_037543.1	P54819-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	AK2	ENST00000672715.1	MANE Select	c.25G>C	p.Glu9Gln	missense	Exon 1 of 6	ENSP00000499935.1	P54819-1
	AK2	ENST00000373449.7	TSL:1	c.25G>C	p.Glu9Gln	missense	Exon 1 of 7	ENSP00000362548.2	P54819-2
	AK2	ENST00000354858.11	TSL:1	c.25G>C	p.Glu9Gln	missense	Exon 1 of 5	ENSP00000346921.7	A0A5K1VW67

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.089
BayesDel_addAF	Benign	-0.042	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	16
DANN	Uncertain	0.98
DEOGEN2	Benign	0.018	T
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.77
FATHMM_MKL	Benign	0.76	D
LIST_S2	Uncertain	0.90	D
M_CAP	Benign	0.042	D
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	0.60	N
PhyloP100		0.57
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.17
Sift	Benign	0.28	T
Sift4G	Benign	0.25	T
Polyphen		0.81	P
Vest4		0.26
MutPred		0.14		Loss of glycosylation at P10 (P = 0.0757)
MVP		0.64
MPC		0.29
ClinPred		0.15	T
GERP RS		0.87
PromoterAI		0.0052	Neutral
Varity_R		0.17
gMVP		0.67
Mutation Taster		=94/6	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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

Other links and lift over

dbSNP: rs267606647; hg19: chr1-33502405;