rs7143186

Variant names:

• chr14-50246961-T-A
• rs7143186
• NM_024884.3:c.*97A>T

Your query was ambiguous. Multiple possible variants found:

• chr14-50246961-T-A
• chr14-50246961-T-C
• chr14-50246961-T-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_024884.3(L2HGDH):​c.*97A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000854 in 152,304 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as (no stars).

• Frequency:
  • Genomes: 𝑓 0.000085 (1 hom., cov: 32)
  • Exomes 𝑓: 0.000089 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: L2HGDH NM_024884.3 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.530
• Publications: 5 publications found

Genes affected

L2HGDH (HGNC:20499): (L-2-hydroxyglutarate dehydrogenase) This gene encodes L-2-hydroxyglutarate dehydrogenase, a FAD-dependent enzyme that oxidizes L-2-hydroxyglutarate to alpha-ketoglutarate in a variety of mammalian tissues. Mutations in this gene cause L-2-hydroxyglutaric aciduria, a rare autosomal recessive neurometabolic disorder resulting in moderate to severe cognitive disability. [provided by RefSeq, Jul 2008]

L2HGDH Gene-Disease associations (from GenCC):

• L-2-hydroxyglutaric aciduria

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet
• mitochondrial disease

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_024884.3. 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
	L2HGDH	NM_024884.3	MANE Select	c.*97A>T		3_prime_UTR	Exon 10 of 10	NP_079160.1	Q9H9P8-1
	L2HGDH	NM_001425214.1		c.*97A>T		3_prime_UTR	Exon 11 of 11	NP_001412143.1
	L2HGDH	NM_001425215.1		c.*97A>T		3_prime_UTR	Exon 12 of 12	NP_001412144.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	L2HGDH	ENST00000267436.9	TSL:1 MANE Select	c.*97A>T		3_prime_UTR	Exon 10 of 10	ENSP00000267436.4	Q9H9P8-1
	L2HGDH	ENST00000261699.8	TSL:1	c.1197-9236A>T		intron	N/A	ENSP00000261699.4	C9JVN9
	L2HGDH	ENST00000889799.1		c.*97A>T		3_prime_UTR	Exon 11 of 11	ENSP00000559858.1

Frequencies

GnomAD3 genomes AF: 0.0000854 AC: 13 AN: 152186 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000622

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000890 AC: 117 AN: 1314688 Hom.: 0 Cov.: 21 AF XY: 0.000138 AC XY: 89 AN XY: 644832

African (AFR) AF: 0.0000346 AC: 1 AN: 28928

American (AMR) AF: 0.000366 AC: 10 AN: 27288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22910

East Asian (EAS) AF: 0.00 AC: 0 AN: 36044

South Asian (SAS) AF: 0.00142 AC: 101 AN: 70930

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3770

European-Non Finnish (NFE) AF: 0.00000196 AC: 2 AN: 1022744

Other (OTH) AF: 0.0000551 AC: 3 AN: 54452

GnomAD4 genome AF: 0.0000854 AC: 13 AN: 152304 Hom.: 1 Cov.: 32 AF XY: 0.000148 AC XY: 11 AN XY: 74454

African (AFR) AF: 0.00 AC: 0 AN: 41566

American (AMR) AF: 0.000654 AC: 10 AN: 15286

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10610

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

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68042

Other (OTH) AF: 0.00 AC: 0 AN: 2116

Alfa AF: 0.00 Hom.: 57970

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	3.9
DANN	Benign	0.22
PhyloP100		-0.53

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.060		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: rs7143186; hg19: chr14-50713679;