rs2066100851

Variant names:

• chr15-72755567-T-C
• rs2066100851
• NM_001365225.1:c.928A>G

Variant summary

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

The NM_001365225.1(ADPGK):​c.928A>G​(p.Ile310Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I310T) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: ADPGK NM_001365225.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.83
• Publications: 0 publications found

Genes affected

ADPGK (HGNC:25250): (ADP dependent glucokinase) ADPGK (EC 2.7.1.147) catalyzes the ADP-dependent phosphorylation of glucose to glucose-6-phosphate and may play a role in glycolysis, possibly during ischemic conditions (Ronimus and Morgan, 2004 [PubMed 14975750]).[supplied by OMIM, Mar 2008]

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=0.23129323).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365225.1. 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
	ADPGK	NM_001365225.1	MANE Select	c.928A>G	p.Ile310Val	missense	Exon 6 of 7	NP_001352154.1	Q9BRR6-1
	ADPGK	NM_031284.5		c.928A>G	p.Ile310Val	missense	Exon 6 of 7	NP_112574.3
	ADPGK	NM_001365226.1		c.562A>G	p.Ile188Val	missense	Exon 6 of 7	NP_001352155.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ADPGK	ENST00000456471.3	TSL:1 MANE Select	c.928A>G	p.Ile310Val	missense	Exon 6 of 7	ENSP00000397694.3	Q9BRR6-1
	ADPGK	ENST00000562621.1	TSL:1	n.3044A>G		non_coding_transcript_exon	Exon 1 of 2
	ADPGK	ENST00000567941.5	TSL:1	n.*904A>G		non_coding_transcript_exon	Exon 6 of 7	ENSP00000458102.1	Q9BRR6-6

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

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

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.086
BayesDel_addAF	Benign	-0.16	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	18
DANN	Benign	0.97
Eigen	Benign	-0.12
Eigen_PC	Benign	-0.000074
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Benign	0.75	T
M_CAP	Benign	0.0078	T
MetaRNN	Benign	0.23	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.7	L
PhyloP100		3.8
PrimateAI	Uncertain	0.51	T
PROVEAN	Benign	-0.49	N
REVEL	Benign	0.084
Sift	Benign	0.49	T
Sift4G	Benign	0.41	T
Polyphen		0.34	B
Vest4		0.25
MutPred		0.74		Gain of disorder (P = 0.1109)
MVP		0.52
MPC		0.21
ClinPred		0.33	T
GERP RS		3.7
gMVP		0.39

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

Other links and lift over

dbSNP: rs2066100851; hg19: chr15-73047908;