Genetic Variant GDPD2:p.His274Gln (chrX-70427349-C-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_017711.4(GDPD2):c.822C>G(p.His274Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000912 in 1,096,541 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. 14/20 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: -0.324

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 made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.06426078).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GDPD2	NM_017711.4 link	c.822C>G	p.His274Gln	missense_variant	Exon 10 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.822C>G	p.His274Gln	missense_variant	Exon 10 of 16	1	NM_017711.4	ENSP00000363503.3		Q9HCC8-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

9.12e-7

AC:

AN:

1096541

Hom.:

Cov.:

AF XY:

0.00000276

AC XY:

AN XY:

361919

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000119

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jan 03, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.822C>G (p.H274Q) alteration is located in exon 10 (coding exon 9) of the GDPD2 gene. This alteration results from a C to G substitution at nucleotide position 822, causing the histidine (H) at amino acid position 274 to be replaced by a glutamine (Q). 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

-0.52

BayesDel_noAF

Benign

-0.99

CADD

Benign

DANN

Benign

0.90

DEOGEN2

Benign

0.0058

.;.;.;T

FATHMM_MKL

Benign

0.043

LIST_S2

Benign

0.77

T;.;T;T

M_CAP

Benign

0.0050

MetaRNN

Benign

0.064

T;T;T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.29

N;.;.;N

PrimateAI

Benign

0.31

PROVEAN

Benign

0.040

N;N;N;N

REVEL

Benign

0.025

Sift

Benign

0.48

T;T;T;T

Sift4G

Benign

0.50

T;T;T;T

Polyphen

0.0010

.;.;.;B

Vest4

0.18

MutPred

0.40

Loss of disorder (P = 0.1879);.;.;Loss of disorder (P = 0.1879);

MVP

0.27

MPC

0.42

ClinPred

0.031

GERP RS

-1.2

Varity_R

0.065

gMVP

0.59

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.090

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over