Genetic Variant GDPD2:p.Arg150Cys (chrX-70426455-C-T) – ACMG Classification: Likely_benign (-6 pts)

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_017711.4(GDPD2):c.448C>T(p.Arg150Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000158 in 1,205,322 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 6 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000027 ( 0 hom., 0 hem., cov: 24)

Exomes 𝑓: 0.000015 ( 0 hom. 6 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.426

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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.08605221).

BS2

High Hemizygotes in GnomAdExome4 at 6 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.448C>T	p.Arg150Cys	missense	Exon 6 of 16	NP_060181.2
GDPD2	NM_001171192.2		c.448C>T	p.Arg150Cys	missense	Exon 6 of 17	NP_001164663.1	Q9HCC8-3
GDPD2	NM_001171191.2		c.211C>T	p.Arg71Cys	missense	Exon 4 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.448C>T	p.Arg150Cys	missense	Exon 6 of 16	ENSP00000363503.3	Q9HCC8-1
GDPD2	ENST00000453994.6	TSL:2	c.448C>T	p.Arg150Cys	missense	Exon 6 of 17	ENSP00000414019.2	Q9HCC8-3
GDPD2	ENST00000913685.1		c.448C>T	p.Arg150Cys	missense	Exon 6 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes

AF:

0.0000267

AC:

AN:

112512

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000564

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000275

AC:

AN:

181776

AF XY:

0.0000452

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000732

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:

0.0000146

AC:

AN:

1092810

Hom.:

Cov.:

AF XY:

0.0000167

AC XY:

AN XY:

358400

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26317

American (AMR)

AF:

0.0000569

AC:

AN:

35176

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

19348

East Asian (EAS)

AF:

0.00

AC:

AN:

30179

South Asian (SAS)

AF:

0.000148

AC:

AN:

53910

European-Finnish (FIN)

AF:

0.00

AC:

AN:

40484

Middle Eastern (MID)

AF:

0.00

AC:

AN:

4110

European-Non Finnish (NFE)

AF:

0.00000717

AC:

AN:

837382

Other (OTH)

AF:

0.00

AC:

AN:

45904

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.460

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome 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

GnomAD4 genome

AF:

0.0000267

AC:

AN:

112512

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

34680

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30965

American (AMR)

AF:

0.00

AC:

AN:

10715

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2651

East Asian (EAS)

AF:

0.00

AC:

AN:

3581

South Asian (SAS)

AF:

0.00

AC:

AN:

2707

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6218

Middle Eastern (MID)

AF:

0.00

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0000564

AC:

AN:

53233

Other (OTH)

AF:

0.00

AC:

AN:

1517

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.558

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:

0.000142

Hom.:

Bravo

AF:

0.0000264

ExAC

AF:

0.0000165

AC:

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

0.12

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.62

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.071

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.85

M_CAP

Benign

0.033

MetaRNN

Benign

0.086

MetaSVM

Benign

-0.97

MutationAssessor

Uncertain

2.3

PhyloP100

0.43

PrimateAI

Benign

0.29

PROVEAN

Benign

-1.3

REVEL

Benign

0.085

Sift

Benign

0.17

Sift4G

Benign

0.18

Polyphen

1.0

Vest4

0.13

MutPred

0.46

Gain of catalytic residue at S152 (P = 0.0891)

MVP

0.48

MPC

0.57

ClinPred

0.26

GERP RS

3.5

Varity_R

0.14

gMVP

0.49

Mutation Taster

=99/1

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

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