Genetic Variant GDPD2:p.Leu170Ile (chrX-70426693-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_017711.4(GDPD2):c.508C>A(p.Leu170Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000182 in 1,095,938 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 1 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 23)

Exomes 𝑓: 0.0000018 ( 0 hom. 1 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.383

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 Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07327369).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD2	NM_017711.4 link	c.508C>A	p.Leu170Ile	missense_variant	Exon 7 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.508C>A	p.Leu170Ile	missense_variant	Exon 7 of 16	1	NM_017711.4	ENSP00000363503.3		Q9HCC8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.0000111

AC:

AN:

180920

Hom.:

AF XY:

0.0000152

AC XY:

AN XY:

65612

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000734

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000182

AC:

AN:

1095938

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361350

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000569

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Feb 23, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.508C>A (p.L170I) alteration is located in exon 7 (coding exon 6) of the GDPD2 gene. This alteration results from a C to A substitution at nucleotide position 508, causing the leucine (L) at amino acid position 170 to be replaced by an isoleucine (I). 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

0.087

BayesDel_addAF

Benign

-0.51

BayesDel_noAF

Benign

-0.78

CADD

Benign

DANN

Benign

0.96

DEOGEN2

Benign

0.016

.;.;.;T

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.59

T;.;T;T

M_CAP

Benign

0.0035

MetaRNN

Benign

0.073

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.3

L;.;.;L

PrimateAI

Benign

0.31

PROVEAN

Benign

-0.43

N;N;N;N

REVEL

Benign

0.032

Sift

Benign

0.21

T;T;T;T

Sift4G

Benign

0.21

T;T;T;T

Polyphen

0.0090

.;.;.;B

Vest4

0.27

MutPred

0.21

Gain of catalytic residue at L170 (P = 0.0486);.;.;Gain of catalytic residue at L170 (P = 0.0486);

MVP

0.39

MPC

0.50

ClinPred

0.068

GERP RS

1.1

Varity_R

0.071

gMVP

0.48

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.080

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