2-142989395-G-A

Variant names:

• chr2-142989395-G-A
• rs1050951
• ENST00000375773.6:c.*92G>A

Variant summary

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

The ENST00000375773.6(KYNU):​c.*92G>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.122 in 988,814 control chromosomes in the GnomAD database, including 7,614 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 0.11 (1078 hom., cov: 32)
  • Exomes 𝑓: 0.12 (6536 hom.)
• Consequence: KYNU ENST00000375773.6 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.14
• Publications: 13 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

ACMG classification

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

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.68).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.248 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KYNU	NM_003937.3	c.902+3374G>A		intron_variant	Intron 10 of 13	ENST00000264170.9	NP_003928.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KYNU	ENST00000375773.6	c.*92G>A		3_prime_UTR_variant	Exon 12 of 12	1		ENSP00000364928.2
KYNU	ENST00000264170.9	c.902+3374G>A		intron_variant	Intron 10 of 13	1	NM_003937.3	ENSP00000264170.4
KYNU	ENST00000409512.5	c.902+3374G>A		intron_variant	Intron 11 of 14	1		ENSP00000386731.1

Frequencies

GnomAD3 genomes AF: 0.114 AC: 17331 AN: 151730 Hom.: 1076 Cov.: 32

Gnomad AFR AF: 0.113

Gnomad AMI AF: 0.0921

Gnomad AMR AF: 0.0912

Gnomad ASJ AF: 0.0650

Gnomad EAS AF: 0.259

Gnomad SAS AF: 0.135

Gnomad FIN AF: 0.0721

Gnomad MID AF: 0.0981

Gnomad NFE AF: 0.117

Gnomad OTH AF: 0.112

GnomAD4 exome AF: 0.123 AC: 102926 AN: 836966 Hom.: 6536 Cov.: 26 AF XY: 0.122 AC XY: 47393 AN XY: 386890

African (AFR) AF: 0.109 AC: 1726 AN: 15798

American (AMR) AF: 0.0824 AC: 167 AN: 2026

Ashkenazi Jewish (ASJ) AF: 0.0634 AC: 330 AN: 5206

East Asian (EAS) AF: 0.280 AC: 1079 AN: 3854

South Asian (SAS) AF: 0.129 AC: 2193 AN: 17036

European-Finnish (FIN) AF: 0.0641 AC: 20 AN: 312

Middle Eastern (MID) AF: 0.0826 AC: 134 AN: 1622

European-Non Finnish (NFE) AF: 0.123 AC: 93618 AN: 763666

Other (OTH) AF: 0.133 AC: 3659 AN: 27446

GnomAD4 genome AF: 0.114 AC: 17343 AN: 151848 Hom.: 1078 Cov.: 32 AF XY: 0.113 AC XY: 8352 AN XY: 74234

African (AFR) AF: 0.113 AC: 4679 AN: 41462

American (AMR) AF: 0.0916 AC: 1394 AN: 15214

Ashkenazi Jewish (ASJ) AF: 0.0650 AC: 225 AN: 3462

East Asian (EAS) AF: 0.259 AC: 1334 AN: 5146

South Asian (SAS) AF: 0.134 AC: 648 AN: 4822

European-Finnish (FIN) AF: 0.0721 AC: 764 AN: 10592

Middle Eastern (MID) AF: 0.0918 AC: 27 AN: 294

European-Non Finnish (NFE) AF: 0.117 AC: 7948 AN: 67836

Other (OTH) AF: 0.114 AC: 240 AN: 2108

Alfa AF: 0.115 Hom.: 285

Bravo AF: 0.115

Asia WGS AF: 0.191 AC: 663 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.68
CADD	Benign	6.2
DANN	Benign	0.80
PhyloP100		1.1
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: rs1050951; hg19: chr2-143746964; COSMIC: COSV51585354;