chr2-241734937-C-G

Position:

• chr2-241734937-C-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_152783.5(D2HGDH):​c.-92-196C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0205 in 393,738 control chromosomes in the GnomAD database, including 136 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.019 (36 hom., cov: 34)
  • Exomes 𝑓: 0.021 (100 hom.)
• Consequence: D2HGDH NM_152783.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.27

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]

ENSG00000215692 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.75).
• BP6: Variant 2-241734937-C-G is Benign according to our data. Variant chr2-241734937-C-G is described in ClinVar as [Benign]. Clinvar id is 1263894.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0192 (2920/152198) while in subpopulation NFE AF= 0.0264 (1798/67982). AF 95% confidence interval is 0.0254. There are 36 homozygotes in gnomad4. There are 1486 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 36 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
D2HGDH	NM_152783.5	c.-92-196C>G		intron_variant		ENST00000321264.9	NP_689996.4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
D2HGDH	ENST00000321264.9	c.-92-196C>G		intron_variant		1	NM_152783.5	ENSP00000315351.4

Frequencies

GnomAD3 genomes AF: 0.0192 AC: 2920 AN: 152090 Hom.: 36 Cov.: 34

Gnomad AFR AF: 0.00490

Gnomad AMI AF: 0.00768

Gnomad AMR AF: 0.0194

Gnomad ASJ AF: 0.0104

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00103

Gnomad FIN AF: 0.0502

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0264

Gnomad OTH AF: 0.0196

GnomAD4 exome AF: 0.0213 AC: 5137 AN: 241540 Hom.: 100 AF XY: 0.0205 AC XY: 2539 AN XY: 124032

Gnomad4 AFR exome AF: 0.00520

Gnomad4 AMR exome AF: 0.0162

Gnomad4 ASJ exome AF: 0.0101

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00164

Gnomad4 FIN exome AF: 0.0419

Gnomad4 NFE exome AF: 0.0248

Gnomad4 OTH exome AF: 0.0178

GnomAD4 genome AF: 0.0192 AC: 2920 AN: 152198 Hom.: 36 Cov.: 34 AF XY: 0.0200 AC XY: 1486 AN XY: 74402

Gnomad4 AFR AF: 0.00488

Gnomad4 AMR AF: 0.0194

Gnomad4 ASJ AF: 0.0104

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00103

Gnomad4 FIN AF: 0.0502

Gnomad4 NFE AF: 0.0264

Gnomad4 OTH AF: 0.0194

Alfa AF: 0.00832 Hom.: 2

Bravo AF: 0.0163

Asia WGS AF: 0.000579 AC: 2 AN: 3470

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	-0.75
CADD	Benign	4.7
DANN	Benign	0.67

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: rs113276310; hg19: chr2-242674352;