4-37840164-C-A

Position:

• chr4-37840164-C-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018290.4(PGM2):​c.624C>A​(p.Asp208Glu) 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. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGM2 NM_018290.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.938

Genes affected

PGM2 (HGNC:8906): (phosphoglucomutase 2) Enables phosphopentomutase activity. Predicted to be involved in carbohydrate metabolic process and deoxyribose phosphate catabolic process. Predicted to act upstream of or within glucose metabolic process. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.08940843).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
PGM2	NM_018290.4	c.624C>A	p.Asp208Glu	missense_variant	6/14	ENST00000381967.9	NP_060760.2
PGM2	XM_047415895.1	c.207C>A	p.Asp69Glu	missense_variant	3/11		XP_047271851.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
PGM2	ENST00000381967.9	c.624C>A	p.Asp208Glu	missense_variant	6/14	1	NM_018290.4	ENSP00000371393.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000282 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Aug 19, 2024

The c.624C>A (p.D208E) alteration is located in exon 6 (coding exon 6) of the PGM2 gene. This alteration results from a C to A substitution at nucleotide position 624, causing the aspartic acid (D) at amino acid position 208 to be replaced by a glutamic acid (E). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.16
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	0.0030
DANN	Benign	0.84
DEOGEN2	Uncertain	0.61	D
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.16	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.024	T
MetaRNN	Benign	0.089	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.4	L
PrimateAI	Benign	0.35	T
PROVEAN	Benign	-1.9	N
REVEL	Benign	0.077
Sift	Benign	0.22	T
Sift4G	Benign	0.092	T
Polyphen		0.0010	B
Vest4		0.25
MutPred		0.35		Gain of catalytic residue at D208 (P = 0.1472);
MVP		0.21
MPC		0.051
ClinPred		0.11	T
GERP RS		-9.6
Varity_R		0.035
gMVP		0.52

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: rs750611272; hg19: chr4-37841786;