Variant chr2-27094472-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The ENST00000260599.11(KHK):c.210-5A>G variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0105 in 1,613,080 control chromosomes in the GnomAD database, including 1,521 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/2 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.057 ( 833 hom., cov: 33)

Exomes 𝑓: 0.0056 ( 688 hom. )

Consequence

KHK
ENST00000260599.11 splice_region, splice_polypyrimidine_tract, intron

Scores

Splicing: ADA: 0.001299

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 2.35

Variant links:

Genes affected

KHK (HGNC:6315): (ketohexokinase) This gene encodes ketohexokinase that catalyzes conversion of fructose to fructose-1-phosphate. The product of this gene is the first enzyme with a specialized pathway that catabolizes dietary fructose. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

KHK links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.49).

BP6

Variant 2-27094472-A-G is Benign according to our data. Variant chr2-27094472-A-G is described in ClinVar as [Benign]. Clinvar id is 335485.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.195 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
KHK	NM_006488.3 linkuse as main transcript	c.210-328A>G		intron_variant		ENST00000260598.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KHK	ENST00000260598.10 linkuse as main transcript	c.210-328A>G		intron_variant		2	NM_006488.3	P3	P50053-1

Frequencies

GnomAD3 genomes

AF:

0.0571

AC:

8677

AN:

151952

Hom.:

828

Cov.:

show subpopulations

Gnomad AFR

AF:

0.198

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0221

Gnomad ASJ

AF:

0.00144

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.000485

Gnomad OTH

AF:

0.0455

GnomAD3 exomes

AF:

0.0145

AC:

3645

AN:

251086

Hom.:

315

AF XY:

0.0103

AC XY:

1394

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.200

Gnomad AMR exome

AF:

0.00882

Gnomad ASJ exome

AF:

0.000497

Gnomad EAS exome

AF:

0.0000544

Gnomad SAS exome

AF:

0.000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000299

Gnomad OTH exome

AF:

0.00798

GnomAD4 exome

AF:

0.00563

AC:

8223

AN:

1461010

Hom.:

688

Cov.:

AF XY:

0.00476

AC XY:

3458

AN XY:

726832

show subpopulations

Gnomad4 AFR exome

AF:

0.199

Gnomad4 AMR exome

AF:

0.0110

Gnomad4 ASJ exome

AF:

0.000459

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.000487

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000164

Gnomad4 OTH exome

AF:

0.0127

GnomAD4 genome

AF:

0.0573

AC:

8712

AN:

152070

Hom.:

833

Cov.:

AF XY:

0.0545

AC XY:

4052

AN XY:

74322

show subpopulations

Gnomad4 AFR

AF:

0.199

Gnomad4 AMR

AF:

0.0221

Gnomad4 ASJ

AF:

0.00144

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000485

Gnomad4 OTH

AF:

0.0450

Alfa

AF:

0.0272

Hom.:

187

Bravo

AF:

0.0658

Asia WGS

AF:

0.00895

AC:

AN:

3478

EpiCase

AF:

0.000654

EpiControl

AF:

0.000178

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

- -

Essential fructosuria

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jan 13, 2018

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

DANN

Benign

0.84

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.0013

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over