X-70427167-C-T

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_017711.4(GDPD2):​c.733C>T​(p.Arg245Trp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000498 in 1,205,115 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 4 hemizygotes in GnomAD. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 23)
Exomes 𝑓: 0.0000037 ( 0 hom. 3 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

3
4
10

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.275
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High Hemizygotes in GnomAdExome4 at 3 gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GDPD2NM_017711.4 linkc.733C>T p.Arg245Trp missense_variant Exon 9 of 16 ENST00000374382.4 NP_060181.2 Q9HCC8-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDPD2ENST00000374382.4 linkc.733C>T p.Arg245Trp missense_variant Exon 9 of 16 1 NM_017711.4 ENSP00000363503.3 Q9HCC8-1

Frequencies

GnomAD3 genomes
AF:
0.0000180
AC:
2
AN:
111281
Hom.:
0
Cov.:
23
AF XY:
0.0000299
AC XY:
1
AN XY:
33481
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000191
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000545
AC:
1
AN:
183349
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
67783
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000524
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000366
AC:
4
AN:
1093834
Hom.:
0
Cov.:
30
AF XY:
0.00000835
AC XY:
3
AN XY:
359368
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000185
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000358
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000180
AC:
2
AN:
111281
Hom.:
0
Cov.:
23
AF XY:
0.0000299
AC XY:
1
AN XY:
33481
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.000191
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
ExAC
AF:
0.00000824
AC:
1

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
May 23, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.733C>T (p.R245W) alteration is located in exon 9 (coding exon 8) of the GDPD2 gene. This alteration results from a C to T substitution at nucleotide position 733, causing the arginine (R) at amino acid position 245 to be replaced by a tryptophan (W). 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
0.13
BayesDel_addAF
Benign
-0.24
T
BayesDel_noAF
Benign
-0.44
CADD
Benign
22
DANN
Pathogenic
1.0
DEOGEN2
Benign
0.11
.;.;.;T
FATHMM_MKL
Benign
0.35
N
LIST_S2
Uncertain
0.95
D;.;D;D
M_CAP
Pathogenic
0.60
D
MetaRNN
Uncertain
0.59
D;D;D;D
MetaSVM
Benign
-0.31
T
MutationAssessor
Benign
1.9
L;.;.;L
PrimateAI
Benign
0.48
T
PROVEAN
Pathogenic
-4.5
D;D;D;D
REVEL
Benign
0.21
Sift
Uncertain
0.0020
D;D;D;D
Sift4G
Uncertain
0.0060
D;D;D;D
Polyphen
1.0
.;.;.;D
Vest4
0.19
MutPred
0.66
Loss of disorder (P = 0.0071);.;.;Loss of disorder (P = 0.0071);
MVP
0.75
MPC
1.3
ClinPred
0.92
D
GERP RS
2.5
Varity_R
0.42
gMVP
0.84

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.

Other links and lift over

dbSNP: rs752164164; hg19: chrX-69647017; COSMIC: COSV65533789; COSMIC: COSV65533789; API