chr2-142988925-C-G

Variant names:

• chr2-142988925-C-G
• rs10496935
• NM_003937.3:c.902+2904C>G

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+2904C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.222 in 1,558,488 control chromosomes in the GnomAD database, including 42,147 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 0.26 (5799 hom., cov: 32)
  • Exomes 𝑓: 0.22 (36348 hom.)
• Consequence: KYNU NM_003937.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0970
• Publications: 10 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: Labcorp Genetics (formerly Invitae), Laboratory for Molecular Medicine, 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=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.458 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003937.3. 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
	KYNU	NM_003937.3	MANE Select	c.902+2904C>G		intron	N/A	NP_003928.1	Q16719-1
	KYNU	NM_001199241.2		c.902+2904C>G		intron	N/A	NP_001186170.1	Q16719-1
	KYNU	NM_001032998.2		c.*38+21C>G		intron	N/A	NP_001028170.1	Q16719-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KYNU	ENST00000264170.9	TSL:1 MANE Select	c.902+2904C>G		intron	N/A	ENSP00000264170.4	Q16719-1
	KYNU	ENST00000409512.5	TSL:1	c.902+2904C>G		intron	N/A	ENSP00000386731.1	Q16719-1
	KYNU	ENST00000375773.6	TSL:1	c.*38+21C>G		intron	N/A	ENSP00000364928.2	Q16719-2

Frequencies

GnomAD3 genomes AF: 0.262 AC: 39670 AN: 151616 Hom.: 5787 Cov.: 32

Gnomad AFR AF: 0.375

Gnomad AMI AF: 0.144

Gnomad AMR AF: 0.205

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.473

Gnomad SAS AF: 0.324

Gnomad FIN AF: 0.216

Gnomad MID AF: 0.231

Gnomad NFE AF: 0.199

Gnomad OTH AF: 0.236

GnomAD4 exome AF: 0.217 AC: 305547 AN: 1406754 Hom.: 36348 Cov.: 24 AF XY: 0.221 AC XY: 155111 AN XY: 702846

African (AFR) AF: 0.373 AC: 11947 AN: 32014

American (AMR) AF: 0.191 AC: 8479 AN: 44456

Ashkenazi Jewish (ASJ) AF: 0.161 AC: 4139 AN: 25710

East Asian (EAS) AF: 0.476 AC: 18677 AN: 39218

South Asian (SAS) AF: 0.318 AC: 26935 AN: 84794

European-Finnish (FIN) AF: 0.215 AC: 11427 AN: 53162

Middle Eastern (MID) AF: 0.244 AC: 1374 AN: 5620

European-Non Finnish (NFE) AF: 0.196 AC: 208865 AN: 1063482

Other (OTH) AF: 0.235 AC: 13704 AN: 58298

GnomAD4 genome AF: 0.262 AC: 39713 AN: 151734 Hom.: 5799 Cov.: 32 AF XY: 0.264 AC XY: 19611 AN XY: 74156

African (AFR) AF: 0.375 AC: 15528 AN: 41392

American (AMR) AF: 0.205 AC: 3129 AN: 15232

Ashkenazi Jewish (ASJ) AF: 0.164 AC: 567 AN: 3460

East Asian (EAS) AF: 0.473 AC: 2424 AN: 5120

South Asian (SAS) AF: 0.324 AC: 1562 AN: 4822

European-Finnish (FIN) AF: 0.216 AC: 2281 AN: 10580

Middle Eastern (MID) AF: 0.207 AC: 61 AN: 294

European-Non Finnish (NFE) AF: 0.199 AC: 13527 AN: 67818

Other (OTH) AF: 0.239 AC: 503 AN: 2106

Alfa AF: 0.129 Hom.: 213

Bravo AF: 0.264

Asia WGS AF: 0.375 AC: 1303 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	3.0
DANN	Benign	0.46
PhyloP100		0.097
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: rs10496935; hg19: chr2-143746494; COSMIC: COSV51594113;