rs2116665

Positions:

• chr2-156549737-G-A

Variant summary

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

The NM_000408.5(GPD2):​c.791G>A​(p.Arg264His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.694 in 1,612,688 control chromosomes in the GnomAD database, including 391,350 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

• Frequency:
  • Genomes: 𝑓 0.64 (32457 hom., cov: 34)
  • Exomes 𝑓: 0.70 (358893 hom.)
• Consequence: GPD2 NM_000408.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.02

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 (MetaRNN=2.9374814E-6).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.78 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD2	NM_000408.5	c.791G>A	p.Arg264His	missense_variant	7/17	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.791G>A	p.Arg264His	missense_variant	7/17	1	NM_000408.5	ENSP00000409708.2

Frequencies

GnomAD3 genomes AF: 0.645 AC: 98050 AN: 152034 Hom.: 32442 Cov.: 34

Gnomad AFR AF: 0.487

Gnomad AMI AF: 0.731

Gnomad AMR AF: 0.690

Gnomad ASJ AF: 0.748

Gnomad EAS AF: 0.800

Gnomad SAS AF: 0.671

Gnomad FIN AF: 0.635

Gnomad MID AF: 0.782

Gnomad NFE AF: 0.711

Gnomad OTH AF: 0.662

GnomAD3 exomes AF: 0.691 AC: 173223 AN: 250714 Hom.: 60546 AF XY: 0.693 AC XY: 93865 AN XY: 135472

Gnomad AFR exome AF: 0.474

Gnomad AMR exome AF: 0.735

Gnomad ASJ exome AF: 0.748

Gnomad EAS exome AF: 0.799

Gnomad SAS exome AF: 0.665

Gnomad FIN exome AF: 0.638

Gnomad NFE exome AF: 0.702

Gnomad OTH exome AF: 0.707

GnomAD4 exome AF: 0.699 AC: 1021169 AN: 1460536 Hom.: 358893 Cov.: 44 AF XY: 0.699 AC XY: 508057 AN XY: 726646

Gnomad4 AFR exome AF: 0.475

Gnomad4 AMR exome AF: 0.729

Gnomad4 ASJ exome AF: 0.748

Gnomad4 EAS exome AF: 0.798

Gnomad4 SAS exome AF: 0.670

Gnomad4 FIN exome AF: 0.642

Gnomad4 NFE exome AF: 0.705

Gnomad4 OTH exome AF: 0.699

GnomAD4 genome AF: 0.645 AC: 98100 AN: 152152 Hom.: 32457 Cov.: 34 AF XY: 0.644 AC XY: 47884 AN XY: 74388

Gnomad4 AFR AF: 0.486

Gnomad4 AMR AF: 0.690

Gnomad4 ASJ AF: 0.748

Gnomad4 EAS AF: 0.801

Gnomad4 SAS AF: 0.672

Gnomad4 FIN AF: 0.635

Gnomad4 NFE AF: 0.711

Gnomad4 OTH AF: 0.663

Alfa AF: 0.688 Hom.: 26207

Bravo AF: 0.645

TwinsUK AF: 0.716 AC: 2656

ALSPAC AF: 0.703 AC: 2708

ESP6500AA AF: 0.475 AC: 2093

ESP6500EA AF: 0.710 AC: 6102

ExAC AF: 0.682 AC: 82844

Asia WGS AF: 0.707 AC: 2461 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.59	T
BayesDel_noAF	Benign	-0.47
CADD	Benign	14
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.44	T;T;T;T;.
Eigen	Benign	-0.45
Eigen_PC	Benign	-0.41
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.60	.;.;T;.;T
MetaRNN	Benign	0.0000029	T;T;T;T;T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	1.4	L;L;.;L;.
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.6	N;N;N;N;.
REVEL	Benign	0.058
Sift	Benign	0.082	T;T;T;T;.
Sift4G	Benign	0.18	T;T;T;T;T
Polyphen		0.020	B;B;.;B;.
Vest4		0.072
MPC		0.29
ClinPred		0.011	T
GERP RS		3.2
Varity_R		0.038
gMVP		0.52

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: rs2116665; hg19: chr2-157406249; COSMIC: COSV60090369;