2-156496063-A-C

Position:

• chr2-156496063-A-C

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_000408.5(GPD2):​c.122A>C​(p.Lys41Thr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/23 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GPD2 NM_000408.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.80

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPD2	NM_000408.5	c.122A>C	p.Lys41Thr	missense_variant	3/17	ENST00000438166.7	NP_000399.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPD2	ENST00000438166.7	c.122A>C	p.Lys41Thr	missense_variant	3/17	1	NM_000408.5	ENSP00000409708	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 16, 2024

The c.122A>C (p.K41T) alteration is located in exon 3 (coding exon 2) of the GPD2 gene. This alteration results from a A to C substitution at nucleotide position 122, causing the lysine (K) at amino acid position 41 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.091
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	21
DANN	Benign	0.94
DEOGEN2	Benign	0.15	.;T;T;T;T
Eigen	Benign	-0.33
Eigen_PC	Benign	-0.11
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.69	T;.;.;T;.
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.17	T;T;T;T;T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.0	.;N;N;.;N
MutationTaster	Benign	1.0	D;N;N;N;N
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-0.26	N;N;N;N;N
REVEL	Benign	0.12
Sift	Benign	0.23	T;T;T;T;T
Sift4G	Benign	0.49	T;T;T;T;T
Polyphen		0.0	.;B;B;.;B
Vest4		0.27, 0.27, 0.25
MutPred		0.50		Loss of ubiquitination at K41 (P = 0.0183);Loss of ubiquitination at K41 (P = 0.0183);Loss of ubiquitination at K41 (P = 0.0183);Loss of ubiquitination at K41 (P = 0.0183);Loss of ubiquitination at K41 (P = 0.0183);
MVP		0.56
MPC		0.28
ClinPred		0.45	T
GERP RS		5.6
Varity_R		0.10
gMVP		0.42

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.32		Details are displayed if max score is > 0.2
DS_AG_spliceai		0.32		Position offset: 3

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-157352575;