rs121918407

Positions:

• chr2-156579109-T-A
• chr2-156579109-T-C

Variant summary

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

The NM_000408.5(GPD2):​c.1904T>A​(p.Phe635Tyr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPD2 NM_000408.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 7.99

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.1904T>A	p.Phe635Tyr	missense_variant	15/17	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.1904T>A	p.Phe635Tyr	missense_variant	15/17	1	NM_000408.5	ENSP00000409708	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 28

GnomAD4 genome Cov.: 32

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.57
BayesDel_addAF	Uncertain	0.16	D
BayesDel_noAF	Uncertain	-0.010
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.39	T;T;T;.
Eigen	Pathogenic	0.73
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.88	.;.;.;D
M_CAP	Uncertain	0.094	D
MetaRNN	Uncertain	0.67	D;D;D;D
MetaSVM	Uncertain	-0.045	T
MutationAssessor	Pathogenic	3.0	M;M;M;.
MutationTaster	Benign	1.0	D;D;D;D;D
PrimateAI	Uncertain	0.77	T
PROVEAN	Benign	-1.3	N;N;N;.
REVEL	Uncertain	0.43
Sift	Uncertain	0.0090	D;D;D;.
Sift4G	Uncertain	0.050	T;T;T;T
Polyphen		0.96	D;D;D;.
Vest4		0.76
MutPred		0.54		Gain of methylation at K640 (P = 0.0444);Gain of methylation at K640 (P = 0.0444);Gain of methylation at K640 (P = 0.0444);.;
MVP		0.79
MPC		0.62
ClinPred		0.96	D
GERP RS		5.9
Varity_R		0.51
gMVP		0.69

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

LitVar

Other links and lift over

dbSNP: rs121918407; hg19: chr2-157435621;