chr2-142989280-C-A

Variant names:

• chr2-142989280-C-A
• rs1050950
• NM_003937.3:c.902+3259C>A

Variant summary

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

The NM_003937.3(KYNU):​c.902+3259C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.24 in 636,074 control chromosomes in the GnomAD database, including 20,938 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 0.30 (8349 hom., cov: 32)
  • Exomes 𝑓: 0.22 (12589 hom.)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.874
• Publications: 14 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=-0.88).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KYNU	NM_003937.3	c.902+3259C>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	ENST00000264170.9	c.902+3259C>A		intron_variant	Intron 10 of 13	1	NM_003937.3	ENSP00000264170.4
KYNU	ENST00000409512.5	c.902+3259C>A		intron_variant	Intron 11 of 14	1		ENSP00000386731.1
KYNU	ENST00000375773.6	c.*39-62C>A		intron_variant	Intron 11 of 11	1		ENSP00000364928.2

Frequencies

GnomAD3 genomes AF: 0.304 AC: 46121 AN: 151468 Hom.: 8330 Cov.: 32

Gnomad AFR AF: 0.499

Gnomad AMI AF: 0.146

Gnomad AMR AF: 0.229

Gnomad ASJ AF: 0.190

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.222

Gnomad MID AF: 0.259

Gnomad NFE AF: 0.211

Gnomad OTH AF: 0.274

GnomAD4 exome AF: 0.220 AC: 106718 AN: 484486 Hom.: 12589 AF XY: 0.221 AC XY: 51400 AN XY: 232062

African (AFR) AF: 0.509 AC: 4628 AN: 9098

American (AMR) AF: 0.214 AC: 880 AN: 4104

Ashkenazi Jewish (ASJ) AF: 0.174 AC: 674 AN: 3874

East Asian (EAS) AF: 0.451 AC: 2148 AN: 4758

South Asian (SAS) AF: 0.312 AC: 4996 AN: 16000

European-Finnish (FIN) AF: 0.203 AC: 444 AN: 2184

Middle Eastern (MID) AF: 0.235 AC: 241 AN: 1026

European-Non Finnish (NFE) AF: 0.207 AC: 88532 AN: 426902

Other (OTH) AF: 0.252 AC: 4175 AN: 16540

GnomAD4 genome AF: 0.305 AC: 46186 AN: 151588 Hom.: 8349 Cov.: 32 AF XY: 0.306 AC XY: 22682 AN XY: 74062

African (AFR) AF: 0.499 AC: 20619 AN: 41334

American (AMR) AF: 0.229 AC: 3486 AN: 15218

Ashkenazi Jewish (ASJ) AF: 0.190 AC: 659 AN: 3462

East Asian (EAS) AF: 0.473 AC: 2427 AN: 5130

South Asian (SAS) AF: 0.324 AC: 1562 AN: 4818

European-Finnish (FIN) AF: 0.222 AC: 2344 AN: 10558

Middle Eastern (MID) AF: 0.241 AC: 71 AN: 294

European-Non Finnish (NFE) AF: 0.211 AC: 14304 AN: 67762

Other (OTH) AF: 0.277 AC: 581 AN: 2100

Alfa AF: 0.225 Hom.: 7149

Bravo AF: 0.311

Asia WGS AF: 0.385 AC: 1338 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	0.16
DANN	Benign	0.44
PhyloP100		-0.87
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: rs1050950; hg19: chr2-143746849;