Genetic Variant GDPD2:p.Thr334Met (chrX-70429557-C-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.1001C>T(p.Thr334Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0001 in 1,206,906 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 33 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 (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., 1 hem., cov: 22)

Exomes 𝑓: 0.00010 ( 0 hom. 32 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.279

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:

ENSG00000284391 (HGNC:):

ENSG00000284391 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.013724923).

BS2

High Hemizygotes in GnomAdExome4 at 32 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD2	NM_017711.4 link	c.1001C>T	p.Thr334Met	missense_variant	Exon 11 of 16	ENST00000374382.4	NP_060181.2	Q9HCC8-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GDPD2	ENST00000374382.4 link	c.1001C>T	p.Thr334Met	missense_variant	Exon 11 of 16	1	NM_017711.4	ENSP00000363503.3		Q9HCC8-1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111801

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

33971

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000944

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000380

Gnomad FIN

AF:

0.00115

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000565

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.000186

AC:

AN:

183091

Hom.:

AF XY:

0.000192

AC XY:

AN XY:

67575

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000365

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000144

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00100

Gnomad NFE exome

AF:

0.000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000995

AC:

109

AN:

1095051

Hom.:

Cov.:

AF XY:

0.0000888

AC XY:

AN XY:

360523

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.000142

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000166

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00113

Gnomad4 NFE exome

AF:

0.0000477

Gnomad4 OTH exome

AF:

0.000283

GnomAD4 genome

AF:

0.000107

AC:

AN:

111855

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34035

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.0000943

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000381

Gnomad4 FIN

AF:

0.00115

Gnomad4 NFE

AF:

0.0000565

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000670

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 28, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1001C>T (p.T334M) alteration is located in exon 11 (coding exon 10) of the GDPD2 gene. This alteration results from a C to T substitution at nucleotide position 1001, causing the threonine (T) at amino acid position 334 to be replaced by a methionine (M). 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

0.077

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.98

CADD

Benign

6.0

DANN

Benign

0.97

DEOGEN2

Benign

0.046

.;.;.;T

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.60

T;.;T;T

M_CAP

Benign

0.0089

MetaRNN

Benign

0.014

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

L;.;.;L

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.0

D;D;D;D

REVEL

Benign

0.024

Sift

Benign

0.065

T;T;T;T

Sift4G

Uncertain

0.054

T;T;T;T

Polyphen

0.086

.;.;.;B

Vest4

0.093

MVP

0.36

MPC

0.53

ClinPred

0.038

GERP RS

0.38

Varity_R

0.052

gMVP

0.63

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