2-142877384-A-G

Variant names:

• chr2-142877384-A-G
• rs1465839
• ENST00000797297.1:n.66+62T>C

Variant summary

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

The ENST00000797297.1(ENSG00000303809):​n.66+62T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.546 in 151,472 control chromosomes in the GnomAD database, including 23,495 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 0.55 (23495 hom., cov: 31)
  • Exomes 𝑓: 0.25 (0 hom.)
• Consequence: ENSG00000303809 ENST00000797297.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.775
• Publications: 2 publications found

Genes affected

ENSG00000303809 (HGNC:):

KYNU (HGNC:6469): (kynureninase) Kynureninase is a pyridoxal-5'-phosphate (pyridoxal-P) dependent enzyme that catalyzes the cleavage of L-kynurenine and L-3-hydroxykynurenine into anthranilic and 3-hydroxyanthranilic acids, respectively. Kynureninase is involved in the biosynthesis of NAD cofactors from tryptophan through the kynurenine pathway. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2010]

KYNU Gene-Disease associations (from GenCC):

• vertebral, cardiac, renal, and limb defects syndrome 2

  Inheritance: AR Classification: DEFINITIVE, STRONG, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, ClinGen
• encephalopathy due to hydroxykynureninuria

  Inheritance: AR Classification: STRONG, SUPPORTIVE, LIMITED Submitted by: Ambry Genetics, Orphanet, Labcorp Genetics (formerly Invitae)
• congenital vertebral-cardiac-renal anomalies syndrome

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.692 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000797297.1. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	ENSG00000303809	ENST00000797297.1		n.66+62T>C		intron	N/A
	ENSG00000303809	ENST00000797298.1		n.68+62T>C		intron	N/A
	KYNU	ENST00000852077.1		c.-458A>G		upstream_gene	N/A	ENSP00000522136.1

Frequencies

GnomAD3 genomes AF: 0.545 AC: 82543 AN: 151352 Hom.: 23455 Cov.: 31

Gnomad AFR AF: 0.699

Gnomad AMI AF: 0.521

Gnomad AMR AF: 0.595

Gnomad ASJ AF: 0.423

Gnomad EAS AF: 0.547

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.508

Gnomad MID AF: 0.394

Gnomad NFE AF: 0.445

Gnomad OTH AF: 0.504

GnomAD4 exome AF: 0.250 AC: 1 AN: 4 Hom.: 0 AF XY: 0.250 AC XY: 1 AN XY: 4

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AC: 0 AN: 0

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AC: 0 AN: 0

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.250 AC: 1 AN: 4

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.546 AC: 82632 AN: 151468 Hom.: 23495 Cov.: 31 AF XY: 0.552 AC XY: 40868 AN XY: 74004

African (AFR) AF: 0.699 AC: 28835 AN: 41274

American (AMR) AF: 0.596 AC: 9071 AN: 15228

Ashkenazi Jewish (ASJ) AF: 0.423 AC: 1462 AN: 3458

East Asian (EAS) AF: 0.547 AC: 2807 AN: 5128

South Asian (SAS) AF: 0.683 AC: 3292 AN: 4822

European-Finnish (FIN) AF: 0.508 AC: 5323 AN: 10484

Middle Eastern (MID) AF: 0.386 AC: 112 AN: 290

European-Non Finnish (NFE) AF: 0.445 AC: 30190 AN: 67784

Other (OTH) AF: 0.510 AC: 1069 AN: 2096

Alfa AF: 0.499 Hom.: 3145

Bravo AF: 0.560

Asia WGS AF: 0.646 AC: 2245 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.50
DANN	Benign	0.52
PhyloP100		-0.78
PromoterAI		-0.055	Neutral

Splicing

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: rs1465839;

hg19: chr2-143634953;