rs61750965

Positions:

• chr1-33021406-C-A
• chr1-33021406-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001625.4(AK2):​c.386G>T​(p.Ser129Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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. S129N) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 31)
• Consequence: AK2 NM_001625.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.40

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
AK2	NM_001625.4	c.386G>T	p.Ser129Ile	missense_variant	4/6	ENST00000672715.1	NP_001616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
AK2	ENST00000672715.1	c.386G>T	p.Ser129Ile	missense_variant	4/6		NM_001625.4	ENSP00000499935	P3
	ENST00000427524.1	n.246-9629C>A		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Uncertain	0.019	T
BayesDel_noAF	Benign	-0.21
CADD	Benign	22
DANN	Uncertain	0.98
DEOGEN2	Uncertain	0.51	.;D;D;D;.
Eigen	Benign	-0.0032
Eigen_PC	Benign	0.14
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.029	D
MetaRNN	Uncertain	0.51	D;D;D;D;D
MetaSVM	Benign	-0.48	T
MutationAssessor	Benign	0.52	N;.;.;N;.
MutationTaster	Benign	0.99	D;D;D;D;D;D
PrimateAI	Benign	0.40	T
PROVEAN	Uncertain	-3.2	D;D;D;D;D
REVEL	Uncertain	0.34
Sift	Benign	0.11	T;T;T;T;T
Sift4G	Benign	0.17	T;T;T;T;T
Polyphen		0.12	B;B;.;B;.
Vest4		0.60
MutPred		0.39		Loss of disorder (P = 0.0206);.;Loss of disorder (P = 0.0206);Loss of disorder (P = 0.0206);Loss of disorder (P = 0.0206);
MVP		0.77
MPC		0.36
ClinPred		0.48	T
GERP RS		4.4
Varity_R		0.35
gMVP		0.62

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: rs61750965; hg19: chr1-33487007;