Variant chr2-169735805-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_StrongBS1BS2

The ENST00000392647.7(KLHL23):c.791A>G(p.His264Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00175 in 1,614,144 control chromosomes in the GnomAD database, including 64 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0052 ( 22 hom., cov: 33)

Exomes 𝑓: 0.0014 ( 42 hom. )

Consequence

KLHL23
ENST00000392647.7 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 3.19

Variant links:

Genes affected

KLHL23 (HGNC:27506): (kelch like family member 23)

KLHL23 links:

PHOSPHO2-KLHL23 (HGNC:):

PHOSPHO2-KLHL23 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=0.0036722422).

BP6

Variant 2-169735805-A-G is Benign according to our data. Variant chr2-169735805-A-G is described in ClinVar as [Benign]. Clinvar id is 791119.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population amr. gnomad4 allele frequency = 0.00518 (789/152322) while in subpopulation AMR AF= 0.0472 (722/15298). AF 95% confidence interval is 0.0443. There are 22 homozygotes in gnomad4. There are 461 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 22 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL23	NM_144711.6 linkuse as main transcript	c.791A>G	p.His264Arg	missense_variant	2/4	ENST00000392647.7	NP_653312.2	Q8NBE8
PHOSPHO2-KLHL23	NM_001199290.3 linkuse as main transcript	c.791A>G	p.His264Arg	missense_variant	4/6		NP_001186219.1	Q8NBE8
PHOSPHO2-KLHL23	NR_144936.2 linkuse as main transcript	n.359-5580A>G		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL23	ENST00000392647.7 linkuse as main transcript	c.791A>G	p.His264Arg	missense_variant	2/4	1	NM_144711.6	ENSP00000376419.2		Q8NBE8

Frequencies

GnomAD3 genomes

AF:

0.00520

AC:

791

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0474

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000103

Gnomad OTH

AF:

0.00431

GnomAD3 exomes

AF:

0.00590

AC:

1482

AN:

251212

Hom.:

AF XY:

0.00483

AC XY:

656

AN XY:

135872

show subpopulations

Gnomad AFR exome

AF:

0.000870

Gnomad AMR exome

AF:

0.0412

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000272

Gnomad SAS exome

AF:

0.0000327

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000528

Gnomad OTH exome

AF:

0.00523

GnomAD4 exome

AF:

0.00139

AC:

2028

AN:

1461822

Hom.:

Cov.:

AF XY:

0.00123

AC XY:

898

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000508

Gnomad4 AMR exome

AF:

0.0415

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0000927

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000225

Gnomad4 OTH exome

AF:

0.00171

GnomAD4 genome

AF:

0.00518

AC:

789

AN:

152322

Hom.:

Cov.:

AF XY:

0.00619

AC XY:

461

AN XY:

74492

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.0472

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000103

Gnomad4 OTH

AF:

0.00426

Alfa

AF:

0.0318

Hom.:

2345

Bravo

AF:

0.00716

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00383

AC:

465

Asia WGS

AF:

0.00202

AC:

AN:

3478

EpiCase

AF:

0.0000545

EpiControl

AF:

0.00

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Mar 30, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.73

DEOGEN2

Benign

0.017

T;T;.

Eigen

Benign

-0.49

Eigen_PC

Benign

-0.25

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.59

.;T;T

MetaRNN

Benign

0.0037

T;T;T

MetaSVM

Benign

-0.99

MutationAssessor

Benign

0.0

N;N;.

PrimateAI

Uncertain

0.51

PROVEAN

Benign

0.54

N;N;N

REVEL

Benign

0.093

Sift

Benign

0.70

T;T;T

Sift4G

Benign

0.35

T;T;T

Polyphen

0.0

B;B;.

Vest4

0.15

MVP

0.54

MPC

0.12

ClinPred

0.011

GERP RS

3.5

Varity_R

0.081

gMVP

0.35

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