Genetic Variant KLF2:p.Met51Thr (chr19-16325292-T-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016270.4(KLF2):c.152T>C(p.Met51Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000736 in 1,358,494 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.4e-7 ( 0 hom. )

Consequence

KLF2
NM_016270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.55

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

pulmonary arterial hypertension
Inheritance: AD Classification: LIMITED Submitted by: ClinGen

KLF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.19239035).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_016270.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF2	NM_016270.4	MANE Select	c.152T>C	p.Met51Thr	missense	Exon 2 of 3	NP_057354.1	Q9Y5W3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	KLF2	ENST00000248071.6	TSL:1 MANE Select	c.152T>C	p.Met51Thr	missense	Exon 2 of 3	ENSP00000248071.5	Q9Y5W3
	KLF2	ENST00000592003.1	TSL:3	c.75+294T>C		intron	N/A	ENSP00000465035.1	K7EJ60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.36e-7

AC:

AN:

1358494

Hom.:

Cov.:

AF XY:

0.00000149

AC XY:

AN XY:

672002

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27494

American (AMR)

AF:

0.00

AC:

AN:

29764

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

23440

East Asian (EAS)

AF:

0.00

AC:

AN:

30770

South Asian (SAS)

AF:

0.00

AC:

AN:

75896

European-Finnish (FIN)

AF:

0.00

AC:

AN:

42868

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5172

European-Non Finnish (NFE)

AF:

9.37e-7

AC:

AN:

1067120

Other (OTH)

AF:

0.00

AC:

AN:

55970

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.425

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.17

BayesDel_noAF

Benign

-0.49

CADD

Benign

(source)

DANN

Benign

0.92

DEOGEN2

Benign

0.089

Eigen

Benign

-0.42

Eigen_PC

Benign

-0.42

FATHMM_MKL

Uncertain

0.77

LIST_S2

Benign

0.64

M_CAP

Uncertain

0.16

MetaRNN

Benign

0.19

MetaSVM

Benign

-0.97

MutationAssessor

Benign

0.44

PhyloP100

1.5

PrimateAI

Pathogenic

0.97

PROVEAN

Benign

-0.030

REVEL

Benign

0.053

Sift

Benign

0.40

Sift4G

Benign

1.0

Polyphen

0.62

Vest4

0.25

MutPred

0.26

Loss of stability (P = 0.0219)

MVP

0.54

MPC

2.5

ClinPred

0.36

GERP RS

3.0

PromoterAI

-0.0060

Neutral

(source)

Varity_R

0.18

gMVP

0.27

Mutation Taster

=86/14

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over