chr4-103091271-C-T

Position:

• chr4-103091271-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_020139.4(BDH2):​c.263G>A​(p.Gly88Glu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: BDH2 NM_020139.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 7.44

Genes affected

BDH2 (HGNC:32389): (3-hydroxybutyrate dehydrogenase 2) Enables 3-hydroxybutyrate dehydrogenase activity and NAD binding activity. Involved in epithelial cell differentiation and fatty acid beta-oxidation. Located in cytosol. [provided by Alliance of Genome Resources, Apr 2022]

BDH2 (HGNC:):

ACMG classification

Verdict is Uncertain_significance. Variant got 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.877

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
BDH2	NM_020139.4	c.263G>A	p.Gly88Glu	missense_variant	5/10	ENST00000296424.9	NP_064524.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
BDH2	ENST00000296424.9	c.263G>A	p.Gly88Glu	missense_variant	5/10	1	NM_020139.4	ENSP00000296424.4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 29

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

Feb 07, 2023

The c.263G>A (p.G88E) alteration is located in exon 5 (coding exon 4) of the BDH2 gene. This alteration results from a G to A substitution at nucleotide position 263, causing the glycine (G) at amino acid position 88 to be replaced by a glutamic acid (E). 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	Pathogenic	0.91
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	28
DANN	Uncertain	1.0
DEOGEN2	Benign	0.26	T;.;T
Eigen	Pathogenic	0.70
Eigen_PC	Pathogenic	0.68
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Pathogenic	1.0	D;D;D
M_CAP	Uncertain	0.26	D
MetaRNN	Pathogenic	0.88	D;D;D
MetaSVM	Uncertain	0.69	D
MutationAssessor	Benign	1.6	L;.;.
PrimateAI	Uncertain	0.75	T
PROVEAN	Pathogenic	-7.8	D;D;D
REVEL	Pathogenic	0.80
Sift	Pathogenic	0.0	D;D;D
Sift4G	Uncertain	0.024	D;.;.
Polyphen		1.0	D;.;.
Vest4		0.88
MutPred		0.62		Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);Gain of solvent accessibility (P = 0.012);
MVP		0.95
MPC		0.91
ClinPred		1.0	D
GERP RS		4.8
Varity_R		0.98
gMVP		0.80

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

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: chr4-104012428;