dbSNP rs200782055: GDPD2:p.Thr334Met (chrX-70429557-C-T) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -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. 14/21 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

Publications

2 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -8 ACMG points.

BP4

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

BS2

High Hemizygotes in GnomAdExome4 at 32 gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_017711.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDPD2	NM_017711.4	MANE Select	c.1001C>T	p.Thr334Met	missense	Exon 11 of 16	NP_060181.2
GDPD2	NM_001171192.2		c.1001C>T	p.Thr334Met	missense	Exon 11 of 17	NP_001164663.1	Q9HCC8-3
GDPD2	NM_001171191.2		c.764C>T	p.Thr255Met	missense	Exon 9 of 14	NP_001164662.1	Q9HCC8-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GDPD2	ENST00000374382.4	TSL:1 MANE Select	c.1001C>T	p.Thr334Met	missense	Exon 11 of 16	ENSP00000363503.3	Q9HCC8-1
GDPD2	ENST00000453994.6	TSL:2	c.1001C>T	p.Thr334Met	missense	Exon 11 of 17	ENSP00000414019.2	Q9HCC8-3
GDPD2	ENST00000913685.1		c.1001C>T	p.Thr334Met	missense	Exon 11 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes

AF:

0.000107

AC:

AN:

111801

Hom.:

Cov.:

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

GnomAD2 exomes

AF:

0.000186

AC:

AN:

183091

AF XY:

0.000192

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 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

African (AFR)

AF:

0.00

AC:

AN:

26343

American (AMR)

AF:

0.000142

AC:

AN:

35194

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19367

East Asian (EAS)

AF:

0.000166

AC:

AN:

30197

South Asian (SAS)

AF:

0.00

AC:

AN:

54054

European-Finnish (FIN)

AF:

0.00113

AC:

AN:

40531

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4126

European-Non Finnish (NFE)

AF:

0.0000477

AC:

AN:

839230

Other (OTH)

AF:

0.000283

AC:

AN:

46009

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.000107

AC:

AN:

111855

Hom.:

Cov.:

AF XY:

0.0000294

AC XY:

AN XY:

34035

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30822

American (AMR)

AF:

0.0000943

AC:

AN:

10601

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2648

East Asian (EAS)

AF:

0.00

AC:

AN:

3528

South Asian (SAS)

AF:

0.000381

AC:

AN:

2622

European-Finnish (FIN)

AF:

0.00115

AC:

AN:

6084

Middle Eastern (MID)

AF:

0.00

AC:

AN:

219

European-Non Finnish (NFE)

AF:

0.0000565

AC:

AN:

53112

Other (OTH)

AF:

0.00

AC:

AN:

1535

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.507

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0000597

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.000305

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000119

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.077

BayesDel_addAF

Benign

-0.71

BayesDel_noAF

Benign

-0.98

CADD

Benign

6.0

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.046

FATHMM_MKL

Benign

0.058

LIST_S2

Benign

0.60

M_CAP

Benign

0.0089

MetaRNN

Benign

0.014

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.6

PhyloP100

-0.28

PrimateAI

Benign

0.30

PROVEAN

Uncertain

-3.0

REVEL

Benign

0.024

Sift

Benign

0.065

Sift4G

Uncertain

0.054

Polyphen

0.086

Vest4

0.093

MVP

0.36

MPC

0.53

ClinPred

0.038

GERP RS

0.38

Varity_R

0.052

gMVP

0.63

Mutation Taster

=100/0

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over