2-156496164-A-G

Position:

chr2-156496164-A-G

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4_ModerateBP6BS2

The NM_000408.5(GPD2):c.223A>G(p.Ile75Val) variant causes a missense change. The variant allele was found at a frequency of 0.00141 in 1,612,832 control chromosomes in the GnomAD database, including 2 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.00079 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0015 ( 2 hom. )

Consequence

GPD2
NM_000408.5 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1B:1

Conservation

PhyloP100: 6.14

Variant links:

Genes affected

GPD2 (HGNC:4456): (glycerol-3-phosphate dehydrogenase 2) The protein encoded by this gene localizes to the inner mitochondrial membrane and catalyzes the conversion of glycerol-3-phosphate to dihydroxyacetone phosphate, using FAD as a cofactor. Along with GDP1, the encoded protein constitutes the glycerol phosphate shuttle, which reoxidizes NADH formed during glycolysis. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Jan 2010]

GPD2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -7 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06995499).

BP6

Variant 2-156496164-A-G is Benign according to our data. Variant chr2-156496164-A-G is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 3236605.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=1}.

BS2

High Homozygotes in GnomAdExome4 at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD2	NM_000408.5 linkuse as main transcript	c.223A>G	p.Ile75Val	missense_variant	3/17	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7 linkuse as main transcript	c.223A>G	p.Ile75Val	missense_variant	3/17	1	NM_000408.5	ENSP00000409708	P1	P43304-1

Frequencies

GnomAD3 genomes

AF:

0.000789

AC:

120

AN:

152054

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000217

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000284

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00156

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000808

AC:

203

AN:

251100

Hom.:

AF XY:

0.000825

AC XY:

112

AN XY:

135694

show subpopulations

Gnomad AFR exome

AF:

0.000123

Gnomad AMR exome

AF:

0.0000579

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.000277

Gnomad NFE exome

AF:

0.00167

Gnomad OTH exome

AF:

0.000490

GnomAD4 exome

AF:

0.00147

AC:

2150

AN:

1460662

Hom.:

Cov.:

AF XY:

0.00146

AC XY:

1063

AN XY:

726710

show subpopulations

Gnomad4 AFR exome

AF:

0.000239

Gnomad4 AMR exome

AF:

0.000112

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.000131

Gnomad4 NFE exome

AF:

0.00186

Gnomad4 OTH exome

AF:

0.000978

GnomAD4 genome

AF:

0.000789

AC:

120

AN:

152170

Hom.:

Cov.:

AF XY:

0.000739

AC XY:

AN XY:

74420

show subpopulations

Gnomad4 AFR

AF:

0.000217

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000284

Gnomad4 NFE

AF:

0.00156

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.00107

Hom.:

Bravo

AF:

0.000763

TwinsUK

AF:

0.00135

AC:

ALSPAC

AF:

0.00311

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000814

AC:

ExAC

AF:

0.000758

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3476

EpiCase

AF:

0.00142

EpiControl

AF:

0.00148

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Type 2 diabetes mellitus

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Clinical Genomics Laboratory, Washington University in St. Louis

Feb 21, 2024

The GPD2 c.223A>G (p.Ile75Val) variant, to our knowledge, has not been reported in the medical literature. The highest population minor allele frequency in the population database genome aggregation database (v.2.1.1) is 0.16% in the European non-Finnish population. Computational predictors are uncertain as to the impact of this variant on GPD2 function. Due to limited information, and based on ACMG/AMP guidelines for variant interpretation (Richards S et al., PMID: 25741868), the clinical significance of this variant is uncertain at this time. -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jun 01, 2024

GPD2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.078

BayesDel_addAF

Benign

-0.28

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.31

.;T;T;T;T

Eigen

Benign

0.15

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Uncertain

0.89

LIST_S2

Pathogenic

0.98

D;.;.;D;.

M_CAP

Benign

0.049

MetaRNN

Benign

0.070

T;T;T;T;T

MetaSVM

Benign

-0.37

MutationAssessor

Benign

1.2

.;L;L;.;L

MutationTaster

Benign

1.0

D;D;D;D;D

PrimateAI

Uncertain

0.56

PROVEAN

Benign

-0.66

N;N;N;N;N

REVEL

Uncertain

0.42

Sift

Benign

0.17

T;T;T;T;T

Sift4G

Benign

0.26

T;T;T;T;T

Polyphen

0.34

.;B;B;.;B

Vest4

0.37, 0.37, 0.37

MVP

0.49

MPC

0.24

ClinPred

0.048

GERP RS

5.5

Varity_R

0.092

gMVP

0.55

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

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over