Genetic Variant GDPD2:p.Ser332Arg (chrX-70429552-T-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017711.4(GDPD2):c.996T>A(p.Ser332Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000913 in 1,095,647 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. 14/21 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: 9.1e-7 ( 0 hom. 1 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.103

Publications

0 publications found

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:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05803463).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD2	NM_017711.4 link	c.996T>A	p.Ser332Arg	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.996T>A	p.Ser332Arg	missense_variant	Exon 11 of 16	1	NM_017711.4	ENSP00000363503.3		Q9HCC8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000546

AC:

AN:

182987

AF XY:

0.0000148

show subpopulations

Gnomad AFR exome

AF:

0.0000760

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS 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:

9.13e-7

AC:

AN:

1095647

Hom.:

Cov.:

AF XY:

0.00000277

AC XY:

AN XY:

361063

show subpopulations

African (AFR)

AF:

0.0000379

AC:

AN:

26365

American (AMR)

AF:

0.00

AC:

AN:

35192

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19370

East Asian (EAS)

AF:

0.00

AC:

AN:

30189

South Asian (SAS)

AF:

0.00

AC:

AN:

54060

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

839791

Other (OTH)

AF:

0.00

AC:

AN:

46023

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

ExAC

AF:

0.0000165

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Nov 28, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.996T>A (p.S332R) alteration is located in exon 11 (coding exon 10) of the GDPD2 gene. This alteration results from a T to A substitution at nucleotide position 996, causing the serine (S) at amino acid position 332 to be replaced by an arginine (R). 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

0.10

BayesDel_addAF

Benign

-0.64

BayesDel_noAF

Benign

-0.97

CADD

Benign

6.9

(source)

DANN

Uncertain

0.97

DEOGEN2

Benign

0.022

.;.;.;T

FATHMM_MKL

Benign

0.39

LIST_S2

Benign

0.56

T;.;T;T

M_CAP

Benign

0.0023

MetaRNN

Benign

0.058

T;T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Benign

-0.55

N;.;.;N

PhyloP100

-0.10

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.59

N;N;N;N

REVEL

Benign

0.036

Sift

Benign

0.15

T;T;T;T

Sift4G

Benign

0.13

T;T;T;T

Polyphen

0.0

.;.;.;B

Vest4

0.063

MutPred

0.52

Loss of phosphorylation at S332 (P = 0.0363);.;.;Loss of phosphorylation at S332 (P = 0.0363);

MVP

0.24

MPC

0.47

ClinPred

0.047

GERP RS

0.40

Varity_R

0.18

gMVP

0.60

Mutation Taster

=83/17

polymorphism

(source)

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

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X-70429552-T-A

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over