chr2-156496076-C-T

Variant names:

• chr2-156496076-C-T
• NM_000408.5:c.135C>T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6 BP7

The NM_000408.5(GPD2):​c.135C>T​(p.Cys45Cys) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000685 in 1,460,764 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: GPD2 NM_000408.5 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.0560
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 2-156496076-C-T is Benign according to our data. Variant chr2-156496076-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 3048119.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.056 with no splicing effect.

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.135C>T	p.Cys45Cys	synonymous	Exon 3 of 17	NP_000399.3	P43304-1
	GPD2	NM_001083112.3		c.135C>T	p.Cys45Cys	synonymous	Exon 3 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.135C>T	p.Cys45Cys	synonymous	Exon 3 of 17	ENSP00000409708.2	P43304-1
	GPD2	ENST00000310454.10	TSL:1	c.135C>T	p.Cys45Cys	synonymous	Exon 3 of 17	ENSP00000308610.5	P43304-1
	GPD2	ENST00000409674.5	TSL:5	c.135C>T	p.Cys45Cys	synonymous	Exon 3 of 17	ENSP00000386425.1	P43304-1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1460764 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 726762

African (AFR) AF: 0.00 AC: 0 AN: 33444

American (AMR) AF: 0.00 AC: 0 AN: 44714

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26120

East Asian (EAS) AF: 0.00 AC: 0 AN: 39682

South Asian (SAS) AF: 0.00 AC: 0 AN: 86222

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53404

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5686

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111152

Other (OTH) AF: 0.0000166 AC: 1 AN: 60340

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.00144 AC: 5 AN: 3478

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	GPD2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	3.3
DANN	Benign	0.34
PhyloP100		-0.056
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.20		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.20		Position offset: -32

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

hg19: chr2-157352588;