PGD p.Asp244Glu

Variant names:

• chr1-10413139-C-A
• NM_002631.4:c.732C>A
• PGD p.Asp244Glu

Your query was ambiguous. Multiple possible variants found:

• chr1-10413139-C-A
• chr1-10413139-C-G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_002631.4(PGD):​c.732C>A​(p.Asp244Glu) 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 pathogenic outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: PGD NM_002631.4 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.613
• Publications: 0 publications found

Genes affected

PGD (HGNC:8891): (phosphogluconate dehydrogenase) 6-phosphogluconate dehydrogenase is the second dehydrogenase in the pentose phosphate shunt. Deficiency of this enzyme is generally asymptomatic, and the inheritance of this disorder is autosomal dominant. Hemolysis results from combined deficiency of 6-phosphogluconate dehydrogenase and 6-phosphogluconolactonase suggesting a synergism of the two enzymopathies. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Jan 2015]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.899

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_002631.4. 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
	PGD	NM_002631.4	MANE Select	c.732C>A	p.Asp244Glu	missense	Exon 8 of 13	NP_002622.2
	PGD	NM_001304452.2		c.693C>A	p.Asp231Glu	missense	Exon 8 of 13	NP_001291381.1	P52209-2
	PGD	NM_001304451.2		c.666C>A	p.Asp222Glu	missense	Exon 7 of 12	NP_001291380.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	PGD	ENST00000270776.13	TSL:1 MANE Select	c.732C>A	p.Asp244Glu	missense	Exon 8 of 13	ENSP00000270776.8	P52209-1
	PGD	ENST00000863229.1		c.732C>A	p.Asp244Glu	missense	Exon 8 of 13	ENSP00000533288.1
	PGD	ENST00000863230.1		c.729C>A	p.Asp243Glu	missense	Exon 8 of 13	ENSP00000533289.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.71
BayesDel_addAF	Uncertain	0.13	D
BayesDel_noAF	Uncertain	-0.050
CADD	Benign	0.97
DANN	Benign	0.82
DEOGEN2	Benign	0.37	T
Eigen	Benign	-1.5
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.21	N
LIST_S2	Uncertain	0.96	D
M_CAP	Benign	0.020	T
MetaRNN	Pathogenic	0.90	D
MetaSVM	Uncertain	0.066	D
MutationAssessor	Pathogenic	3.1	M
PhyloP100		-0.61
PrimateAI	Uncertain	0.60	T
PROVEAN	Uncertain	-3.4	D
REVEL	Uncertain	0.35
Sift	Benign	0.035	D
Sift4G	Benign	0.11	T
Varity_R		0.68
gMVP		0.86
Mutation Taster		=61/39	polymorphism

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr1-10473196;