2-156476134-C-A

Variant names:

• chr2-156476134-C-A
• rs553714328
• NM_000408.5:c.29C>A

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2 BP4

The NM_000408.5(GPD2):​c.29C>A​(p.Thr10Lys) variant causes a missense change. The variant allele was found at a frequency of 0.000000687 in 1,456,600 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. T10M) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.9e-7 (0 hom.)
• Consequence: GPD2 NM_000408.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 5.15
• Publications: 0 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: Uncertain_significance. The variant received 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.31368107).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000408.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD2	NM_000408.5	MANE Select	c.29C>A	p.Thr10Lys	missense	Exon 2 of 17	NP_000399.3	P43304-1
	GPD2	NM_001083112.3		c.29C>A	p.Thr10Lys	missense	Exon 2 of 17	NP_001076581.2	P43304-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD2	ENST00000438166.7	TSL:1 MANE Select	c.29C>A	p.Thr10Lys	missense	Exon 2 of 17	ENSP00000409708.2	P43304-1
	GPD2	ENST00000310454.10	TSL:1	c.29C>A	p.Thr10Lys	missense	Exon 2 of 17	ENSP00000308610.5	P43304-1
	GPD2	ENST00000409674.5	TSL:5	c.29C>A	p.Thr10Lys	missense	Exon 2 of 17	ENSP00000386425.1	P43304-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.87e-7 AC: 1 AN: 1456600 Hom.: 0 Cov.: 28 AF XY: 0.00000138 AC XY: 1 AN XY: 725008

African (AFR) AF: 0.00 AC: 0 AN: 33374

American (AMR) AF: 0.00 AC: 0 AN: 44718

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26104

East Asian (EAS) AF: 0.00 AC: 0 AN: 39628

South Asian (SAS) AF: 0.00 AC: 0 AN: 86134

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5696

European-Non Finnish (NFE) AF: 9.03e-7 AC: 1 AN: 1107334

Other (OTH) AF: 0.00 AC: 0 AN: 60206

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.38
BayesDel_addAF	Uncertain	0.092	D
BayesDel_noAF	Benign	-0.11
CADD	Benign	22
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Uncertain	0.52
Eigen_PC	Uncertain	0.58
FATHMM_MKL	Uncertain	0.91	D
LIST_S2	Benign	0.85	T
M_CAP	Benign	0.017	T
MetaRNN	Benign	0.31	T
MetaSVM	Benign	-0.84	T
MutationAssessor	Benign	1.7	L
PhyloP100		5.2
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.11
Sift	Benign	0.15	T
Sift4G	Benign	0.35	T
Polyphen		0.86	P
Vest4		0.64
MutPred		0.42		Gain of MoRF binding (P = 0.0251)
MVP		0.74
MPC		0.55
ClinPred		0.86	D
GERP RS		5.9
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.0
Varity_R		0.19
gMVP		0.67
Mutation Taster		=67/33	polymorphism

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: rs553714328; hg19: chr2-157332646;