rs3769357

chr2-156536762-C-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000408.5(GPD2):c.662-12846C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,184 control chromosomes in the GnomAD database, including 1,350 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.13 (1350 hom., cov: 32)
• Consequence: GPD2 NM_000408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPD2	NM_000408.5	c.662-12846C>A		intron_variant		ENST00000438166.7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPD2	ENST00000438166.7	c.662-12846C>A		intron_variant		1	NM_000408.5	P1

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19774 AN: 152066 Hom.: 1349 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.139

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.130 AC: 19784 AN: 152184 Hom.: 1350 Cov.: 32 AF XY: 0.127 AC XY: 9417 AN XY: 74406

Gnomad4 AFR AF: 0.150

Gnomad4 AMR AF: 0.0982

Gnomad4 ASJ AF: 0.131

Gnomad4 EAS AF: 0.0354

Gnomad4 SAS AF: 0.109

Gnomad4 FIN AF: 0.0911

Gnomad4 NFE AF: 0.140

Gnomad4 OTH AF: 0.137

Alfa AF: 0.136 Hom.: 260

Bravo AF: 0.130

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
Cadd	Benign	1.5
Dann	Benign	0.50

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: rs3769357; hg19: chr2-157393274;