chr2-142929263-A-C

Variant names:

• chr2-142929263-A-C
• rs2381356
• NM_003937.3:c.373+1522A>C

Variant summary

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

The ENST00000264170.9(KYNU):​c.373+1522A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.132 in 151,136 control chromosomes in the GnomAD database, including 2,094 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 0.13 (2094 hom., cov: 28)
• Consequence: KYNU ENST00000264170.9 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.252
• Publications: 8 publications found

Genes affected

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: Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), ClinGen
• encephalopathy due to hydroxykynureninuria

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

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ENSG00000303829 (HGNC:):

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.28 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000264170.9. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	NM_003937.3	MANE Select	c.373+1522A>C		intron	N/A	NP_003928.1
	KYNU	NM_001199241.2		c.373+1522A>C		intron	N/A	NP_001186170.1
	KYNU	NM_001032998.2		c.373+1522A>C		intron	N/A	NP_001028170.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	ENST00000264170.9	TSL:1 MANE Select	c.373+1522A>C		intron	N/A	ENSP00000264170.4
	KYNU	ENST00000409512.5	TSL:1	c.373+1522A>C		intron	N/A	ENSP00000386731.1
	KYNU	ENST00000375773.6	TSL:1	c.373+1522A>C		intron	N/A	ENSP00000364928.2

Frequencies

GnomAD3 genomes AF: 0.132 AC: 19973 AN: 151034 Hom.: 2089 Cov.: 28

Gnomad AFR AF: 0.285

Gnomad AMI AF: 0.0615

Gnomad AMR AF: 0.119

Gnomad ASJ AF: 0.0785

Gnomad EAS AF: 0.219

Gnomad SAS AF: 0.123

Gnomad FIN AF: 0.0468

Gnomad MID AF: 0.120

Gnomad NFE AF: 0.0543

Gnomad OTH AF: 0.120

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

GnomAD4 genome AF: 0.132 AC: 19997 AN: 151136 Hom.: 2094 Cov.: 28 AF XY: 0.133 AC XY: 9855 AN XY: 73842

African (AFR) AF: 0.285 AC: 11693 AN: 41064

American (AMR) AF: 0.119 AC: 1809 AN: 15192

Ashkenazi Jewish (ASJ) AF: 0.0785 AC: 272 AN: 3466

East Asian (EAS) AF: 0.218 AC: 1121 AN: 5132

South Asian (SAS) AF: 0.123 AC: 590 AN: 4796

European-Finnish (FIN) AF: 0.0468 AC: 483 AN: 10324

Middle Eastern (MID) AF: 0.113 AC: 33 AN: 292

European-Non Finnish (NFE) AF: 0.0543 AC: 3684 AN: 67870

Other (OTH) AF: 0.122 AC: 256 AN: 2090

Alfa AF: 0.0779 Hom.: 535

Bravo AF: 0.147

Asia WGS AF: 0.177 AC: 613 AN: 3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	1.9
DANN	Benign	0.48
PhyloP100		0.25
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2381356; hg19: chr2-143686832;