rs1268722

Variant names:

• chr10-49743164-G-A
• rs1268722
• NM_018245.3:c.1862-186C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_018245.3(OGDHL):​c.1862-186C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.378 in 152,248 control chromosomes in the GnomAD database, including 13,542 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.38 (13542 hom., cov: 35)
• Consequence: OGDHL NM_018245.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.875
• Publications: 3 publications found

Genes affected

OGDHL (HGNC:25590): (oxoglutarate dehydrogenase L) The protein encoded by this gene is similar to oxoglutarate dehydrogenase (OGDH) of the OGDH complex, which degrades glucose and glutamate. This gene encodes several isoforms, including some that appear to localize to mitochondria. The encoded protein down-regulates the AKT signaling cascade and can suppress the growth of cervical cancer cells. [provided by RefSeq, Dec 2016]

OGDHL Gene-Disease associations (from GenCC):

• Yoon-Bellen neurodevelopmental syndrome

  Inheritance: AR Classification: STRONG, MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018245.3. 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
	OGDHL	NM_018245.3	MANE Select	c.1862-186C>T		intron	N/A	NP_060715.2	Q9ULD0-1
	OGDHL	NM_001347819.1		c.1862-186C>T		intron	N/A	NP_001334748.1	Q9ULD0-1
	OGDHL	NM_001143996.2		c.1691-186C>T		intron	N/A	NP_001137468.1	Q9ULD0-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	OGDHL	ENST00000374103.9	TSL:1 MANE Select	c.1862-186C>T		intron	N/A	ENSP00000363216.4	Q9ULD0-1
	OGDHL	ENST00000852721.1		c.1955-186C>T		intron	N/A	ENSP00000522780.1
	OGDHL	ENST00000852716.1		c.1880-186C>T		intron	N/A	ENSP00000522775.1

Frequencies

GnomAD3 genomes AF: 0.378 AC: 57577 AN: 152132 Hom.: 13543 Cov.: 35

Gnomad AFR AF: 0.111

Gnomad AMI AF: 0.487

Gnomad AMR AF: 0.471

Gnomad ASJ AF: 0.331

Gnomad EAS AF: 0.871

Gnomad SAS AF: 0.411

Gnomad FIN AF: 0.503

Gnomad MID AF: 0.357

Gnomad NFE AF: 0.462

Gnomad OTH AF: 0.396

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.378 AC: 57580 AN: 152248 Hom.: 13542 Cov.: 35 AF XY: 0.383 AC XY: 28472 AN XY: 74436

African (AFR) AF: 0.111 AC: 4603 AN: 41570

American (AMR) AF: 0.470 AC: 7199 AN: 15308

Ashkenazi Jewish (ASJ) AF: 0.331 AC: 1149 AN: 3472

East Asian (EAS) AF: 0.871 AC: 4502 AN: 5166

South Asian (SAS) AF: 0.411 AC: 1983 AN: 4820

European-Finnish (FIN) AF: 0.503 AC: 5337 AN: 10612

Middle Eastern (MID) AF: 0.356 AC: 104 AN: 292

European-Non Finnish (NFE) AF: 0.462 AC: 31415 AN: 67986

Other (OTH) AF: 0.400 AC: 846 AN: 2114

Alfa AF: 0.427 Hom.: 7355

Bravo AF: 0.370

Asia WGS AF: 0.617 AC: 2145 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	5.0
DANN	Benign	0.64
PhyloP100		0.88
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1268722;

hg19: chr10-50951210;