2-156510813-G-C

Position:

• chr2-156510813-G-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000408.5(GPD2):​c.292G>C​(p.Val98Leu) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPD2 NM_000408.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.35

Genes affected

GPD2 (HGNC:4456): (glycerol-3-phosphate dehydrogenase 2) The protein encoded by this gene localizes to the inner mitochondrial membrane and catalyzes the conversion of glycerol-3-phosphate to dihydroxyacetone phosphate, using FAD as a cofactor. Along with GDP1, the encoded protein constitutes the glycerol phosphate shuttle, which reoxidizes NADH formed during glycolysis. Two transcript variants encoding the same protein have been found for this gene.[provided by RefSeq, Jan 2010]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD2	NM_000408.5	c.292G>C	p.Val98Leu	missense_variant	4/17	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.292G>C	p.Val98Leu	missense_variant	4/17	1	NM_000408.5	ENSP00000409708	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Mar 30, 2024

The c.292G>C (p.V98L) alteration is located in exon 4 (coding exon 3) of the GPD2 gene. This alteration results from a G to C substitution at nucleotide position 292, causing the valine (V) at amino acid position 98 to be replaced by a leucine (L). 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	0.23
BayesDel_addAF	Uncertain	0.028	T
BayesDel_noAF	Benign	-0.20
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.66	.;D;D;T;D
Eigen	Uncertain	0.25
Eigen_PC	Uncertain	0.41
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Uncertain	0.96	D;.;.;D;.
M_CAP	Benign	0.0097	T
MetaRNN	Uncertain	0.62	D;D;D;D;D
MetaSVM	Benign	-0.70	T
MutationAssessor	Uncertain	2.1	.;M;M;.;M
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Uncertain	-2.4	N;N;N;D;N
REVEL	Benign	0.24
Sift	Benign	0.16	T;D;D;T;D
Sift4G	Uncertain	0.051	T;D;D;T;D
Polyphen		0.0020	.;B;B;.;B
Vest4		0.46, 0.42
MutPred		0.61		Gain of ubiquitination at K94 (P = 0.1204);Gain of ubiquitination at K94 (P = 0.1204);Gain of ubiquitination at K94 (P = 0.1204);Gain of ubiquitination at K94 (P = 0.1204);Gain of ubiquitination at K94 (P = 0.1204);
MVP		0.72
MPC		0.37
ClinPred		0.92	D
GERP RS		5.7
Varity_R		0.30
gMVP		0.66

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-157367325;