Genetic Variant GDPD2:p.Glu3Asp (chrX-70424993-G-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_017711.4(GDPD2):c.9G>T(p.Glu3Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000381 in 1,077,201 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 27 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/20 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. E3K) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.000038 ( 0 hom. 27 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.31

Variant links:

Genes affected

GDPD2 (HGNC:25974): (glycerophosphodiester phosphodiesterase domain containing 2) This gene encodes a member of the glycerophosphodiester phosphodiesterase enzyme family. The encoded protein hydrolyzes glycerophosphoinositol to produce inositol 1-phosphate and glycerol. This protein may have a role in osteoblast differentiation and growth. Alternate splicing results in multiple transcript variants. [provided by RefSeq, Jan 2010]

GDPD2 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.014802635).

BS2

High Hemizygotes in GnomAdExome4 at 27 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD2	NM_017711.4 link	c.9G>T	p.Glu3Asp	missense_variant	Exon 2 of 16	ENST00000374382.4	NP_060181.2	Q9HCC8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
GDPD2	ENST00000374382.4 link	c.9G>T	p.Glu3Asp	missense_variant	Exon 2 of 16	1	NM_017711.4	ENSP00000363503.3	Q9HCC8-1
GDPD2	ENST00000453994.6 link	c.9G>T	p.Glu3Asp	missense_variant	Exon 2 of 17	2		ENSP00000414019.2	Q9HCC8-3
GDPD2	ENST00000536730.5 link	c.-132-361G>T		intron_variant	Intron 1 of 14	2		ENSP00000445982.1	Q9HCC8-2
GDPD2	ENST00000538649.5 link	c.-28-770G>T		intron_variant	Intron 1 of 13	2		ENSP00000444601.1	Q9HCC8-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.000101

AC:

AN:

148027

Hom.:

AF XY:

0.000203

AC XY:

AN XY:

44339

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000420

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000913

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000381

AC:

AN:

1077201

Hom.:

Cov.:

AF XY:

0.0000774

AC XY:

AN XY:

348755

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000308

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000780

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ExAC

AF:

0.000142

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 04, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.9G>T (p.E3D) alteration is located in exon 2 (coding exon 1) of the GDPD2 gene. This alteration results from a G to T substitution at nucleotide position 9, causing the glutamic acid (E) at amino acid position 3 to be replaced by an aspartic acid (D). 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

0.090

BayesDel_addAF

Benign

-0.75

BayesDel_noAF

Benign

-0.91

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0095

.;T

FATHMM_MKL

Benign

0.12

LIST_S2

Benign

0.60

T;T

M_CAP

Benign

0.063

MetaRNN

Benign

0.015

T;T

MetaSVM

Benign

-0.96

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.30

PROVEAN

Benign

-0.82

N;N

REVEL

Benign

0.11

Sift

Benign

0.38

T;T

Sift4G

Benign

0.44

T;T

Polyphen

0.0

.;B

Vest4

0.048

MutPred

0.13

Loss of glycosylation at P5 (P = 0.0819);Loss of glycosylation at P5 (P = 0.0819);

MVP

0.17

MPC

0.38

ClinPred

0.044

GERP RS

2.1

Varity_R

0.068

gMVP

0.097

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