chr2-27092384-G-A

Position:

chr2-27092384-G-A

Variant summary

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

The NM_006488.3(KHK):c.145G>A(p.Val49Ile) variant causes a missense change. The variant allele was found at a frequency of 0.369 in 1,613,034 control chromosomes in the GnomAD database, including 113,460 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.37 ( 10529 hom., cov: 34)

Exomes 𝑓: 0.37 ( 102931 hom. )

Consequence

KHK
NM_006488.3 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 4.25

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 (MetaRNN=2.3898482E-4).

BP6

Variant 2-27092384-G-A is Benign according to our data. Variant chr2-27092384-G-A is described in ClinVar as [Benign]. Clinvar id is 335482.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.5 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KHK	NM_006488.3 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	2/8	ENST00000260598.10	NP_006479.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KHK	ENST00000260598.10 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	2/8	2	NM_006488.3	ENSP00000260598	P3	P50053-1
KHK	ENST00000260599.11 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	2/8	1		ENSP00000260599	A1	P50053-2
KHK	ENST00000429697.2 linkuse as main transcript	c.145G>A	p.Val49Ile	missense_variant	2/9	5		ENSP00000404741
KHK	ENST00000490823.5 linkuse as main transcript	n.493G>A		non_coding_transcript_exon_variant	4/10	5

Frequencies

GnomAD3 genomes

AF:

0.365

AC:

55547

AN:

152056

Hom.:

10514

Cov.:

show subpopulations

Gnomad AFR

AF:

0.318

Gnomad AMI

AF:

0.532

Gnomad AMR

AF:

0.509

Gnomad ASJ

AF:

0.396

Gnomad EAS

AF:

0.240

Gnomad SAS

AF:

0.307

Gnomad FIN

AF:

0.327

Gnomad MID

AF:

0.345

Gnomad NFE

AF:

0.377

Gnomad OTH

AF:

0.371

GnomAD3 exomes

AF:

0.386

AC:

96856

AN:

250738

Hom.:

20412

AF XY:

0.377

AC XY:

51191

AN XY:

135684

show subpopulations

Gnomad AFR exome

AF:

0.317

Gnomad AMR exome

AF:

0.624

Gnomad ASJ exome

AF:

0.388

Gnomad EAS exome

AF:

0.234

Gnomad SAS exome

AF:

0.311

Gnomad FIN exome

AF:

0.334

Gnomad NFE exome

AF:

0.378

Gnomad OTH exome

AF:

0.392

GnomAD4 exome

AF:

0.370

AC:

540369

AN:

1460860

Hom.:

102931

Cov.:

AF XY:

0.368

AC XY:

267576

AN XY:

726820

show subpopulations

Gnomad4 AFR exome

AF:

0.323

Gnomad4 AMR exome

AF:

0.609

Gnomad4 ASJ exome

AF:

0.396

Gnomad4 EAS exome

AF:

0.218

Gnomad4 SAS exome

AF:

0.313

Gnomad4 FIN exome

AF:

0.334

Gnomad4 NFE exome

AF:

0.373

Gnomad4 OTH exome

AF:

0.360

GnomAD4 genome

AF:

0.365

AC:

55581

AN:

152174

Hom.:

10529

Cov.:

AF XY:

0.365

AC XY:

27182

AN XY:

74386

show subpopulations

Gnomad4 AFR

AF:

0.318

Gnomad4 AMR

AF:

0.510

Gnomad4 ASJ

AF:

0.396

Gnomad4 EAS

AF:

0.240

Gnomad4 SAS

AF:

0.305

Gnomad4 FIN

AF:

0.327

Gnomad4 NFE

AF:

0.377

Gnomad4 OTH

AF:

0.374

Alfa

AF:

0.383

Hom.:

22557

Bravo

AF:

0.383

TwinsUK

AF:

0.357

AC:

1322

ALSPAC

AF:

0.382

AC:

1472

ESP6500AA

AF:

0.318

AC:

1399

ESP6500EA

AF:

0.376

AC:

3231

ExAC

AF:

0.377

AC:

45711

Asia WGS

AF:

0.305

AC:

1061

AN:

3478

EpiCase

AF:

0.388

EpiControl

AF:

0.384

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

AlphaMissense

Benign

0.20

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.40

.;T;D

Eigen

Benign

-0.29

Eigen_PC

Benign

-0.24

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.74

T;T;T

MetaRNN

Benign

0.00024

T;T;T

MetaSVM

Benign

-0.94

MutationAssessor

Uncertain

2.3

M;M;.

MutationTaster

Benign

0.0093

P;P

PrimateAI

Uncertain

0.55

PROVEAN

Benign

-0.84

N;N;N

REVEL

Benign

0.25

Sift

Benign

0.065

T;T;T

Sift4G

Benign

0.078

T;T;T

Polyphen

0.52

P;B;.

Vest4

0.091

MPC

0.27

ClinPred

0.017

GERP RS

2.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.20

gMVP

0.36

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

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