dbSNP rs2229687: PGD:p.Asp244Glu (chr1-10413139-C-G) – ACMG Classification: Uncertain_significance (4 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP3_Moderate

The NM_002631.4(PGD):c.732C>G(p.Asp244Glu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,788 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 𝑓 0.0 ( 0 hom., cov: 32)

Exomes 𝑓: 6.8e-7 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

PGD
NM_002631.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.613

Variant links:

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]

PGD links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 4 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.869

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
PGD	NM_002631.4 link	c.732C>G	p.Asp244Glu	missense_variant	Exon 8 of 13	ENST00000270776.13	NP_002622.2	P52209-1
PGD	NM_001304452.2 link	c.693C>G	p.Asp231Glu	missense_variant	Exon 8 of 13		NP_001291381.1	P52209-2
PGD	NM_001304451.2 link	c.666C>G	p.Asp222Glu	missense_variant	Exon 7 of 12		NP_001291380.1	P52209B4E2U0

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
PGD	ENST00000270776.13 link	c.732C>G	p.Asp244Glu	missense_variant	Exon 8 of 13	1	NM_002631.4	ENSP00000270776.8	P52209-1
PGD	ENST00000460189.1 link	c.654C>G	p.Asp218Glu	missense_variant	Exon 6 of 6	2		ENSP00000467362.1	K7EPF6
PGD	ENST00000483936.5 link	c.297C>G	p.Asp99Glu	missense_variant	Exon 4 of 6	5		ENSP00000466156.1	K7ELN9
PGD	ENST00000493288.1 link	n.306C>G		non_coding_transcript_exon_variant	Exon 1 of 2	3

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

152012

Hom.:

Cov.:

FAILED QC

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251402

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135886

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461788

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727204

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000116

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

152012

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74218

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Uncertain

0.065

BayesDel_noAF

Uncertain

-0.050

CADD

Benign

0.98

DANN

Benign

0.81

DEOGEN2

Benign

0.37

T;T

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.7

FATHMM_MKL

Benign

0.22

LIST_S2

Uncertain

0.96

D;D

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.87

D;D

MetaSVM

Uncertain

0.066

MutationAssessor

Pathogenic

3.1

M;.

PrimateAI

Uncertain

0.60

PROVEAN

Uncertain

-3.4

D;.

REVEL

Uncertain

0.35

Sift

Benign

0.035

D;.

Sift4G

Benign

0.11

T;D

Polyphen

0.19

B;.

Vest4

0.67

MutPred

0.75

Loss of sheet (P = 0.0228);.;

MVP

0.78

MPC

0.32

ClinPred

0.42

GERP RS

-10

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.68

gMVP

0.86

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Computational scores

Splicing

Publications

LitVar

Other links and lift over