Variant rs3745318 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 ENST00000248071.6(KLF2):c.311T>C(p.Leu104Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.76 in 1,405,660 control chromosomes in the GnomAD database, including 409,575 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.81 ( 51016 hom., cov: 33)

Exomes 𝑓: 0.75 ( 358559 hom. )

Consequence

KLF2
ENST00000248071.6 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.813

Variant links:

Genes affected

KLF2 (HGNC:6347): (KLF transcription factor 2) This gene encodes a protein that belongs to the Kruppel family of transcription factors. The encoded zinc finger protein is expressed early in mammalian development and is found in many different cell types. The protein acts to bind the CACCC box found in the promoter of target genes to activate their transcription. It plays a role in many processes during development and disease including adipogenesis, embryonic erythropoiesis, epithelial integrity, inflammation and t-cell viability. [provided by RefSeq, Mar 2017]

KLF2 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=7.106354E-7).

BP6

Variant 19-16325451-T-C is Benign according to our data. Variant chr19-16325451-T-C is described in ClinVar as [Benign]. Clinvar id is 1177685.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.941 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF2	NM_016270.4 linkuse as main transcript	c.311T>C	p.Leu104Pro	missense_variant	2/3	ENST00000248071.6	NP_057354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6 linkuse as main transcript	c.311T>C	p.Leu104Pro	missense_variant	2/3	1	NM_016270.4	ENSP00000248071	P1
KLF2	ENST00000592003.1 linkuse as main transcript	c.75+453T>C		intron_variant		3		ENSP00000465035

Frequencies

GnomAD3 genomes

AF:

0.813

AC:

123106

AN:

151358

Hom.:

50954

Cov.:

show subpopulations

Gnomad AFR

AF:

0.949

Gnomad AMI

AF:

0.804

Gnomad AMR

AF:

0.860

Gnomad ASJ

AF:

0.816

Gnomad EAS

AF:

0.477

Gnomad SAS

AF:

0.756

Gnomad FIN

AF:

0.794

Gnomad MID

AF:

0.888

Gnomad NFE

AF:

0.752

Gnomad OTH

AF:

0.817

GnomAD3 exomes

AF:

0.751

AC:

33283

AN:

44342

Hom.:

12763

AF XY:

0.746

AC XY:

20010

AN XY:

26806

show subpopulations

Gnomad AFR exome

AF:

0.944

Gnomad AMR exome

AF:

0.888

Gnomad ASJ exome

AF:

0.802

Gnomad EAS exome

AF:

0.400

Gnomad SAS exome

AF:

0.730

Gnomad FIN exome

AF:

0.755

Gnomad NFE exome

AF:

0.722

Gnomad OTH exome

AF:

0.813

GnomAD4 exome

AF:

0.754

AC:

945101

AN:

1254192

Hom.:

358559

Cov.:

AF XY:

0.753

AC XY:

464857

AN XY:

617010

show subpopulations

Gnomad4 AFR exome

AF:

0.961

Gnomad4 AMR exome

AF:

0.884

Gnomad4 ASJ exome

AF:

0.817

Gnomad4 EAS exome

AF:

0.479

Gnomad4 SAS exome

AF:

0.752

Gnomad4 FIN exome

AF:

0.782

Gnomad4 NFE exome

AF:

0.752

Gnomad4 OTH exome

AF:

0.754

GnomAD4 genome

AF:

0.814

AC:

123225

AN:

151468

Hom.:

51016

Cov.:

AF XY:

0.814

AC XY:

60208

AN XY:

73996

show subpopulations

Gnomad4 AFR

AF:

0.949

Gnomad4 AMR

AF:

0.860

Gnomad4 ASJ

AF:

0.816

Gnomad4 EAS

AF:

0.478

Gnomad4 SAS

AF:

0.757

Gnomad4 FIN

AF:

0.794

Gnomad4 NFE

AF:

0.752

Gnomad4 OTH

AF:

0.813

Alfa

AF:

0.783

Hom.:

9992

Bravo

AF:

0.826

TwinsUK

AF:

0.760

AC:

2818

ALSPAC

AF:

0.749

AC:

2886

ESP6500AA

AF:

0.950

AC:

1680

ESP6500EA

AF:

0.795

AC:

3452

ExAC

AF:

0.665

AC:

51590

Asia WGS

AF:

0.631

AC:

2119

AN:

3352

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	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 04, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.77

BayesDel_noAF

Benign

-0.74

CADD

Benign

DANN

Benign

0.68

DEOGEN2

Benign

0.050

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.0021

LIST_S2

Benign

0.12

MetaRNN

Benign

7.1e-7

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.34

MutationTaster

Benign

0.99

P;P

PrimateAI

Pathogenic

0.86

PROVEAN

Benign

1.2

REVEL

Benign

0.092

Sift

Benign

0.21

Sift4G

Benign

0.22

Polyphen

0.0

Vest4

0.039

MPC

2.2

ClinPred

0.0085

GERP RS

0.56

Varity_R

0.079

gMVP

0.19

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