chr2-156536762-C-A

Variant names:

• chr2-156536762-C-A
• rs3769357
• NM_000408.5:c.662-12846C>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.662-12846C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 152,184 control chromosomes in the GnomAD database, including 1,350 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 0.13 (1350 hom., cov: 32)
• Consequence: GPD2 NM_000408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.172
• Publications: 3 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=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPD2	NM_000408.5	c.662-12846C>A		intron_variant	Intron 6 of 16	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.662-12846C>A		intron_variant	Intron 6 of 16	1	NM_000408.5	ENSP00000409708.2

Frequencies

GnomAD3 genomes AF: 0.130 AC: 19774 AN: 152066 Hom.: 1349 Cov.: 32

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0549

Gnomad AMR AF: 0.0984

Gnomad ASJ AF: 0.131

Gnomad EAS AF: 0.0351

Gnomad SAS AF: 0.108

Gnomad FIN AF: 0.0911

Gnomad MID AF: 0.127

Gnomad NFE AF: 0.140

Gnomad OTH AF: 0.139

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

GnomAD4 genome AF: 0.130 AC: 19784 AN: 152184 Hom.: 1350 Cov.: 32 AF XY: 0.127 AC XY: 9417 AN XY: 74406

African (AFR) AF: 0.150 AC: 6239 AN: 41512

American (AMR) AF: 0.0982 AC: 1502 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.131 AC: 454 AN: 3468

East Asian (EAS) AF: 0.0354 AC: 183 AN: 5170

South Asian (SAS) AF: 0.109 AC: 526 AN: 4826

European-Finnish (FIN) AF: 0.0911 AC: 967 AN: 10610

Middle Eastern (MID) AF: 0.126 AC: 37 AN: 294

European-Non Finnish (NFE) AF: 0.140 AC: 9537 AN: 67990

Other (OTH) AF: 0.137 AC: 289 AN: 2108

Alfa AF: 0.136 Hom.: 260

Bravo AF: 0.130

Asia WGS AF: 0.0700 AC: 243 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	1.5
DANN	Benign	0.50
PhyloP100		-0.17
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: rs3769357; hg19: chr2-157393274;