chr2-156517100-G-T

Variant names:

• chr2-156517100-G-T
• rs526540
• NM_000408.5:c.661+3604G>T

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+3604G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.701 in 152,074 control chromosomes in the GnomAD database, including 37,482 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 0.70 (37482 hom., cov: 33)
• Consequence: GPD2 NM_000408.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.429
• 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=-0.93).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.786 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+3604G>T		intron	N/A	NP_000399.3
	GPD2	NM_001083112.3		c.661+3604G>T		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+3604G>T		intron	N/A	ENSP00000409708.2
	GPD2	ENST00000310454.10	TSL:1	c.661+3604G>T		intron	N/A	ENSP00000308610.5
	GPD2	ENST00000409674.5	TSL:5	c.661+3604G>T		intron	N/A	ENSP00000386425.1

Frequencies

GnomAD3 genomes AF: 0.700 AC: 106427 AN: 151956 Hom.: 37442 Cov.: 33

Gnomad AFR AF: 0.656

Gnomad AMI AF: 0.732

Gnomad AMR AF: 0.722

Gnomad ASJ AF: 0.753

Gnomad EAS AF: 0.806

Gnomad SAS AF: 0.661

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.813

Gnomad NFE AF: 0.724

Gnomad OTH AF: 0.713

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

GnomAD4 genome AF: 0.701 AC: 106532 AN: 152074 Hom.: 37482 Cov.: 33 AF XY: 0.697 AC XY: 51815 AN XY: 74342

African (AFR) AF: 0.656 AC: 27203 AN: 41478

American (AMR) AF: 0.723 AC: 11056 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.753 AC: 2613 AN: 3472

East Asian (EAS) AF: 0.806 AC: 4159 AN: 5160

South Asian (SAS) AF: 0.662 AC: 3193 AN: 4824

European-Finnish (FIN) AF: 0.632 AC: 6663 AN: 10544

Middle Eastern (MID) AF: 0.820 AC: 241 AN: 294

European-Non Finnish (NFE) AF: 0.724 AC: 49237 AN: 68002

Other (OTH) AF: 0.715 AC: 1507 AN: 2108

Alfa AF: 0.710 Hom.: 7328

Bravo AF: 0.710

Asia WGS AF: 0.719 AC: 2505 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	0.32
DANN	Benign	0.41
PhyloP100		-0.43
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: rs526540; hg19: chr2-157373612;