10-49737844-T-G

Variant names:

• chr10-49737844-T-G
• rs41281971
• NM_018245.3:c.2532A>C

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6 BP7 BS2

The NM_018245.3(OGDHL):​c.2532A>C​(p.Thr844Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00149 in 1,614,004 control chromosomes in the GnomAD database, including 9 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.0014 (1 hom., cov: 33)
  • Exomes 𝑓: 0.0015 (8 hom.)
• Consequence: OGDHL NM_018245.3 synonymous
• Clinical Significance: Likely benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.762
• Publications: 1 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.53).
• BP6: Variant 10-49737844-T-G is Benign according to our data. Variant chr10-49737844-T-G is described in ClinVar as Likely_benign. ClinVar VariationId is 3040480.Status of the report is no_assertion_criteria_provided, 0 stars.
• BP7: Synonymous conserved (PhyloP=-0.762 with no splicing effect.
• BS2: High Homozygotes in GnomAdExome4 at 8 AR gene

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.2532A>C	p.Thr844Thr	synonymous	Exon 20 of 23	NP_060715.2	Q9ULD0-1
	OGDHL	NM_001347819.1		c.2532A>C	p.Thr844Thr	synonymous	Exon 20 of 23	NP_001334748.1	Q9ULD0-1
	OGDHL	NM_001143996.2		c.2361A>C	p.Thr787Thr	synonymous	Exon 19 of 22	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.2532A>C	p.Thr844Thr	synonymous	Exon 20 of 23	ENSP00000363216.4	Q9ULD0-1
	OGDHL	ENST00000852721.1		c.2625A>C	p.Thr875Thr	synonymous	Exon 21 of 24	ENSP00000522780.1
	OGDHL	ENST00000852716.1		c.2550A>C	p.Thr850Thr	synonymous	Exon 20 of 23	ENSP00000522775.1

Frequencies

GnomAD3 genomes AF: 0.00141 AC: 215 AN: 152020 Hom.: 1 Cov.: 33

Gnomad AFR AF: 0.000314

Gnomad AMI AF: 0.0804

Gnomad AMR AF: 0.000327

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00270

Gnomad FIN AF: 0.0000944

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.000478

GnomAD2 exomes AF: 0.00129 AC: 325 AN: 251478 AF XY: 0.00148

Gnomad AFR exome AF: 0.000492

Gnomad AMR exome AF: 0.000347

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00170

Gnomad OTH exome AF: 0.00277

GnomAD4 exome AF: 0.00149 AC: 2183 AN: 1461866 Hom.: 8 Cov.: 31 AF XY: 0.00154 AC XY: 1119 AN XY: 727232

African (AFR) AF: 0.000239 AC: 8 AN: 33480

American (AMR) AF: 0.000358 AC: 16 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.0000383 AC: 1 AN: 26136

East Asian (EAS) AF: 0.00 AC: 0 AN: 39700

South Asian (SAS) AF: 0.00304 AC: 262 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53396

Middle Eastern (MID) AF: 0.00416 AC: 24 AN: 5768

European-Non Finnish (NFE) AF: 0.00160 AC: 1784 AN: 1112008

Other (OTH) AF: 0.00139 AC: 84 AN: 60396

GnomAD4 genome AF: 0.00141 AC: 215 AN: 152138 Hom.: 1 Cov.: 33 AF XY: 0.00148 AC XY: 110 AN XY: 74356

African (AFR) AF: 0.000313 AC: 13 AN: 41512

American (AMR) AF: 0.000327 AC: 5 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5150

South Asian (SAS) AF: 0.00270 AC: 13 AN: 4816

European-Finnish (FIN) AF: 0.0000944 AC: 1 AN: 10598

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00160 AC: 109 AN: 67974

Other (OTH) AF: 0.000473 AC: 1 AN: 2116

Alfa AF: 0.00159 Hom.: 1

Bravo AF: 0.00161

Asia WGS AF: 0.00115 AC: 4 AN: 3478

EpiCase AF: 0.00240

EpiControl AF: 0.00314

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	OGDHL-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.53
CADD	Benign	4.2
DANN	Benign	0.62
PhyloP100		-0.76
Mutation Taster		=91/9	polymorphism

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

Other links and lift over

dbSNP: rs41281971; hg19: chr10-50945890;