rs56051278

Variant names:

• chr2-156525242-A-G
• rs56051278
• NM_000408.5:c.661+11746A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_000408.5(GPD2):​c.661+11746A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.223 in 152,136 control chromosomes in the GnomAD database, including 4,388 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 0.22 (4388 hom., cov: 32)
• Consequence: GPD2 NM_000408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.267
• Publications: 7 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 (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.303 is higher than 0.05.

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.661+11746A>G		intron	N/A	NP_000399.3
	GPD2	NM_001083112.3		c.661+11746A>G		intron	N/A	NP_001076581.2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPD2	ENST00000438166.7	TSL:1 MANE Select	c.661+11746A>G		intron	N/A	ENSP00000409708.2
	GPD2	ENST00000310454.10	TSL:1	c.661+11746A>G		intron	N/A	ENSP00000308610.5
	GPD2	ENST00000409674.5	TSL:5	c.661+11746A>G		intron	N/A	ENSP00000386425.1

Frequencies

GnomAD3 genomes AF: 0.223 AC: 33966 AN: 152018 Hom.: 4391 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.268

Gnomad AMR AF: 0.243

Gnomad ASJ AF: 0.244

Gnomad EAS AF: 0.177

Gnomad SAS AF: 0.316

Gnomad FIN AF: 0.367

Gnomad MID AF: 0.152

Gnomad NFE AF: 0.267

Gnomad OTH AF: 0.225

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

GnomAD4 genome AF: 0.223 AC: 33953 AN: 152136 Hom.: 4388 Cov.: 32 AF XY: 0.228 AC XY: 16987 AN XY: 74348

African (AFR) AF: 0.101 AC: 4175 AN: 41536

American (AMR) AF: 0.243 AC: 3708 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.244 AC: 846 AN: 3472

East Asian (EAS) AF: 0.177 AC: 919 AN: 5182

South Asian (SAS) AF: 0.316 AC: 1525 AN: 4826

European-Finnish (FIN) AF: 0.367 AC: 3871 AN: 10544

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.267 AC: 18150 AN: 67972

Other (OTH) AF: 0.224 AC: 473 AN: 2112

Alfa AF: 0.252 Hom.: 7785

Bravo AF: 0.202

Asia WGS AF: 0.242 AC: 840 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	3.0
DANN	Benign	0.56
PhyloP100		0.27
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: rs56051278; hg19: chr2-157381754;