rs526540

Positions:

• chr2-156517100-G-T

Variant summary

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

The NM_000408.5(GPD2):​c.661+3604G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,074 control chromosomes in the GnomAD database, including 37,482 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 0.70 (37482 hom., cov: 33)
• Consequence: GPD2 NM_000408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429

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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD2	NM_000408.5	c.661+3604G>T		intron_variant		ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.661+3604G>T		intron_variant		1	NM_000408.5	ENSP00000409708	P1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106427 AN: 151956 Hom.: 37442 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.701 AC: 106532 AN: 152074 Hom.: 37482 Cov.: 33 AF XY: 0.697 AC XY: 51815 AN XY: 74342

Gnomad4 AFR AF: 0.656

Gnomad4 AMR AF: 0.723

Gnomad4 ASJ AF: 0.753

Gnomad4 EAS AF: 0.806

Gnomad4 SAS AF: 0.662

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.724

Gnomad4 OTH AF: 0.715

Alfa AF: 0.710 Hom.: 7328

Bravo AF: 0.710

Asia WGS AF: 0.719 AC: 2505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.41

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: rs526540; hg19: chr2-157373612;