X-70427349-C-G

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

17

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]

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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
GDPD2NM_017711.4 linkc.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
GDPD2ENST00000374382.4 linkc.822C>G p.His274Gln missense_variant Exon 10 of 16 1 NM_017711.4 ENSP00000363503.3 Q9HCC8-1

Frequencies

GnomAD3 genomes
Cov.:
23
GnomAD4 exome
AF:
9.12e-7
AC:
1
AN:
1096541
Hom.:
0
Cov.:
30
AF XY:
0.00000276
AC XY:
1
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.:
23

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
T
BayesDel_noAF
Benign
-0.99
CADD
Benign
11
DANN
Benign
0.90
DEOGEN2
Benign
0.0058
.;.;.;T
FATHMM_MKL
Benign
0.043
N
LIST_S2
Benign
0.77
T;.;T;T
M_CAP
Benign
0.0050
T
MetaRNN
Benign
0.064
T;T;T;T
MetaSVM
Benign
-0.98
T
MutationAssessor
Benign
0.29
N;.;.;N
PrimateAI
Benign
0.31
T
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
T
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.

Other links and lift over

hg19: chrX-69647199; API