Variant 4-165299626-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_007246.4(KLHL2):c.891C>G(p.Thr297Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0032 in 1,612,254 control chromosomes in the GnomAD database, including 16 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0029 ( 0 hom., cov: 31)

Exomes 𝑓: 0.0032 ( 16 hom. )

Consequence

KLHL2
NM_007246.4 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.56

Variant links:

Genes affected

KLHL2 (HGNC:6353): (kelch like family member 2) Enables actin binding activity and identical protein binding activity. Predicted to be involved in protein ubiquitination. Located in actin cytoskeleton. [provided by Alliance of Genome Resources, Apr 2022]

KLHL2 links:

KLHL2 (HGNC:):

KLHL2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.62).

BP6

Variant 4-165299626-C-G is Benign according to our data. Variant chr4-165299626-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 2655169.Status of the report is criteria_provided_single_submitter, 1 stars.

BP7

Synonymous conserved (PhyloP=-1.56 with no splicing effect.

BS2

High AC in GnomAd4 at 440 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLHL2	NM_007246.4 linkuse as main transcript	c.891C>G	p.Thr297Thr	synonymous_variant	8/15	ENST00000226725.11	NP_009177.3	O95198-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLHL2	ENST00000226725.11 linkuse as main transcript	c.891C>G	p.Thr297Thr	synonymous_variant	8/15	1	NM_007246.4	ENSP00000226725.6		O95198-1

Frequencies

GnomAD3 genomes

AF:

0.00289

AC:

440

AN:

152124

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00203

Gnomad ASJ

AF:

0.00893

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00373

Gnomad FIN

AF:

0.00208

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.00457

Gnomad OTH

AF:

0.00334

GnomAD3 exomes

AF:

0.00313

AC:

779

AN:

249058

Hom.:

AF XY:

0.00334

AC XY:

450

AN XY:

134726

show subpopulations

Gnomad AFR exome

AF:

0.000494

Gnomad AMR exome

AF:

0.00131

Gnomad ASJ exome

AF:

0.00940

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00290

Gnomad FIN exome

AF:

0.00199

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.00642

GnomAD4 exome

AF:

0.00323

AC:

4718

AN:

1460012

Hom.:

Cov.:

AF XY:

0.00336

AC XY:

2443

AN XY:

726328

show subpopulations

Gnomad4 AFR exome

AF:

0.000719

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.00840

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00278

Gnomad4 FIN exome

AF:

0.00167

Gnomad4 NFE exome

AF:

0.00342

Gnomad4 OTH exome

AF:

0.00358

GnomAD4 genome

AF:

0.00289

AC:

440

AN:

152242

Hom.:

Cov.:

AF XY:

0.00290

AC XY:

216

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.000457

Gnomad4 AMR

AF:

0.00203

Gnomad4 ASJ

AF:

0.00893

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00373

Gnomad4 FIN

AF:

0.00208

Gnomad4 NFE

AF:

0.00457

Gnomad4 OTH

AF:

0.00331

Alfa

AF:

0.00449

Hom.:

Bravo

AF:

0.00275

Asia WGS

AF:

0.00115

AC:

AN:

3478

EpiCase

AF:

0.00591

EpiControl

AF:

0.00451

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Mar 01, 2023

KLHL2: BP4, BP7, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.62

CADD

Benign

4.7

DANN

Benign

0.47

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