dbSNP rs768102716: GDPD2:p.Glu3Lys (chrX-70424991-G-A) – 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.7G>A(p.Glu3Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000104 in 1,186,936 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 31 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 (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. E3D) has been classified as Uncertain significance.

Frequency

Genomes: 𝑓 0.000098 ( 0 hom., 5 hem., cov: 23)

Exomes 𝑓: 0.00011 ( 0 hom. 26 hem. )

Consequence

GDPD2
NM_017711.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.284

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: Benign. The variant received -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.048963875).

BS2

High Hemizygotes in GnomAd4 at 5 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.7G>A	p.Glu3Lys	missense	Exon 2 of 16	NP_060181.2
GDPD2	NM_001171192.2		c.7G>A	p.Glu3Lys	missense	Exon 2 of 17	NP_001164663.1	Q9HCC8-3
GDPD2	NM_001171191.2		c.-28-772G>A		intron	N/A	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.7G>A	p.Glu3Lys	missense	Exon 2 of 16	ENSP00000363503.3	Q9HCC8-1
GDPD2	ENST00000453994.6	TSL:2	c.7G>A	p.Glu3Lys	missense	Exon 2 of 17	ENSP00000414019.2	Q9HCC8-3
GDPD2	ENST00000913685.1		c.7G>A	p.Glu3Lys	missense	Exon 2 of 16	ENSP00000583744.1

Frequencies

GnomAD3 genomes

AF:

0.0000981

AC:

AN:

112111

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:

0.000207

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000341

AC:

AN:

146559

AF XY:

0.00

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 FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000806

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000105

AC:

113

AN:

1074825

Hom.:

Cov.:

AF XY:

0.0000749

AC XY:

AN XY:

346913

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

26078

American (AMR)

AF:

0.0000309

AC:

AN:

32354

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

18772

East Asian (EAS)

AF:

0.00

AC:

AN:

29554

South Asian (SAS)

AF:

0.0000391

AC:

AN:

51097

European-Finnish (FIN)

AF:

0.0000256

AC:

AN:

39128

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3945

European-Non Finnish (NFE)

AF:

0.000123

AC:

102

AN:

828682

Other (OTH)

AF:

0.000155

AC:

AN:

45215

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.457

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:

0.0000981

AC:

AN:

112111

Hom.:

Cov.:

AF XY:

0.000146

AC XY:

AN XY:

34289

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30843

American (AMR)

AF:

0.00

AC:

AN:

10674

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

2654

East Asian (EAS)

AF:

0.00

AC:

AN:

3548

South Asian (SAS)

AF:

0.00

AC:

AN:

2706

European-Finnish (FIN)

AF:

0.00

AC:

AN:

6136

Middle Eastern (MID)

AF:

0.00

AC:

AN:

239

European-Non Finnish (NFE)

AF:

0.000207

AC:

AN:

53135

Other (OTH)

AF:

0.00

AC:

AN:

1499

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome 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

Alfa

AF:

0.000356

Hom.:

Bravo

AF:

0.0000718

ExAC

AF:

0.0000668

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

0.087

BayesDel_addAF

Benign

-0.40

BayesDel_noAF

Benign

-0.81

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.010

FATHMM_MKL

Benign

0.16

LIST_S2

Benign

0.77

M_CAP

Uncertain

0.093

MetaRNN

Benign

0.049

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

PhyloP100

0.28

PrimateAI

Benign

0.34

PROVEAN

Benign

-0.75

REVEL

Benign

0.021

Sift

Benign

0.074

Sift4G

Uncertain

0.039

Polyphen

0.0040

Vest4

0.22

MVP

0.18

MPC

0.47

ClinPred

0.043

GERP RS

2.3

Varity_R

0.10

gMVP

0.21

Mutation Taster

=100/0

polymorphism

(source)

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

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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