2-241734898-A-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_152783.5(D2HGDH):c.-93+203A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 297,032 control chromosomes in the GnomAD database, including 12,622 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.28 (6405 hom., cov: 33)
  • Exomes 𝑓: 0.28 (6217 hom.)
• Consequence: D2HGDH NM_152783.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -6.27

Genes affected

D2HGDH (HGNC:28358): (D-2-hydroxyglutarate dehydrogenase) This gene encodes D-2hydroxyglutarate dehydrogenase, a mitochondrial enzyme belonging to the FAD-binding oxidoreductase/transferase type 4 family. This enzyme, which is most active in liver and kidney but also active in heart and brain, converts D-2-hydroxyglutarate to 2-ketoglutarate. Mutations in this gene are present in D-2-hydroxyglutaric aciduria, a rare recessive neurometabolic disorder causing developmental delay, epilepsy, hypotonia, and dysmorphic features. [provided by RefSeq, Jul 2008]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.86).
• BP6: Variant 2-241734898-A-C is Benign according to our data. Variant chr2-241734898-A-C is described in ClinVar as [Benign]. Clinvar id is 1273444.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
D2HGDH	NM_152783.5	c.-93+203A>C		intron_variant		ENST00000321264.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
D2HGDH	ENST00000321264.9	c.-93+203A>C		intron_variant		1	NM_152783.5	P1
	ENST00000400768.2	n.383-94T>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes AF: 0.284 AC: 43042 AN: 151514 Hom.: 6397 Cov.: 33

Gnomad AFR AF: 0.224

Gnomad AMI AF: 0.442

Gnomad AMR AF: 0.234

Gnomad ASJ AF: 0.396

Gnomad EAS AF: 0.150

Gnomad SAS AF: 0.303

Gnomad FIN AF: 0.319

Gnomad MID AF: 0.316

Gnomad NFE AF: 0.327

Gnomad OTH AF: 0.284

GnomAD4 exome AF: 0.281 AC: 40931 AN: 145410 Hom.: 6217 AF XY: 0.284 AC XY: 20904 AN XY: 73508

Gnomad4 AFR exome AF: 0.217

Gnomad4 AMR exome AF: 0.191

Gnomad4 ASJ exome AF: 0.362

Gnomad4 EAS exome AF: 0.164

Gnomad4 SAS exome AF: 0.210

Gnomad4 FIN exome AF: 0.285

Gnomad4 NFE exome AF: 0.303

Gnomad4 OTH exome AF: 0.278

GnomAD4 genome AF: 0.284 AC: 43061 AN: 151622 Hom.: 6405 Cov.: 33 AF XY: 0.283 AC XY: 20989 AN XY: 74116

Gnomad4 AFR AF: 0.224

Gnomad4 AMR AF: 0.234

Gnomad4 ASJ AF: 0.396

Gnomad4 EAS AF: 0.149

Gnomad4 SAS AF: 0.303

Gnomad4 FIN AF: 0.319

Gnomad4 NFE AF: 0.327

Gnomad4 OTH AF: 0.284

Alfa AF: 0.309 Hom.: 938

Bravo AF: 0.271

Asia WGS AF: 0.219 AC: 757 AN: 3468

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

May 11, 2021

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.80
Dann	Benign	0.13
RBP_binding_hub_radar		0.0
RBP_regulation_power_radar		1.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs79248835; hg19: chr2-242674313;