rs2116665

Variant names:

• chr2-156549737-G-A
• rs2116665
• NM_000408.5:c.791G>A

Variant summary

Our verdict is Benign. The variant received -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. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• 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
• Publications: 38 publications found

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]

GPD2 Gene-Disease associations (from GenCC):

• diabetes mellitus, noninsulin-dependent

  Inheritance: AD Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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 rank	MANE	Protein	UniProt
GPD2	NM_000408.5	c.791G>A	p.Arg264His	missense_variant	Exon 7 of 17	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.791G>A	p.Arg264His	missense_variant	Exon 7 of 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

GnomAD2 exomes AF: 0.691 AC: 173223 AN: 250714 AF XY: 0.693

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 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

African (AFR) AF: 0.475 AC: 15889 AN: 33452

American (AMR) AF: 0.729 AC: 32596 AN: 44710

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 19536 AN: 26124

East Asian (EAS) AF: 0.798 AC: 31641 AN: 39664

South Asian (SAS) AF: 0.670 AC: 57753 AN: 86240

European-Finnish (FIN) AF: 0.642 AC: 34285 AN: 53404

Middle Eastern (MID) AF: 0.739 AC: 4258 AN: 5762

European-Non Finnish (NFE) AF: 0.705 AC: 783039 AN: 1110840

Other (OTH) AF: 0.699 AC: 42172 AN: 60340

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

African (AFR) AF: 0.486 AC: 20167 AN: 41480

American (AMR) AF: 0.690 AC: 10554 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.748 AC: 2594 AN: 3470

East Asian (EAS) AF: 0.801 AC: 4145 AN: 5178

South Asian (SAS) AF: 0.672 AC: 3246 AN: 4830

European-Finnish (FIN) AF: 0.635 AC: 6712 AN: 10564

Middle Eastern (MID) AF: 0.782 AC: 230 AN: 294

European-Non Finnish (NFE) AF: 0.711 AC: 48384 AN: 68020

Other (OTH) AF: 0.663 AC: 1403 AN: 2116

Alfa AF: 0.687 Hom.: 41341

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;.
PhyloP100		2.0
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
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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