Variant 19-16325307-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_016270.4(KLF2):c.167T>C(p.Leu56Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000224 in 1,342,176 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 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: 0.0000022 ( 0 hom. )

Consequence

KLF2
NM_016270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: -0.148

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07632938).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF2	NM_016270.4 link	c.167T>C	p.Leu56Pro	missense_variant	2/3	ENST00000248071.6	NP_057354.1	Q9Y5W3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6 link	c.167T>C	p.Leu56Pro	missense_variant	2/3	1	NM_016270.4	ENSP00000248071.5		Q9Y5W3
KLF2	ENST00000592003.1 link	c.75+309T>C		intron_variant		3		ENSP00000465035.1		K7EJ60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000224

AC:

AN:

1342176

Hom.:

Cov.:

AF XY:

0.00000301

AC XY:

AN XY:

663578

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000134

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000189

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.167T>C (p.L56P) alteration is located in exon 2 (coding exon 2) of the KLF2 gene. This alteration results from a T to C substitution at nucleotide position 167, causing the leucine (L) at amino acid position 56 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.35

BayesDel_addAF

Benign

-0.25

BayesDel_noAF

Benign

-0.60

CADD

Benign

DANN

Benign

0.83

DEOGEN2

Benign

0.081

Eigen

Benign

-0.75

Eigen_PC

Benign

-0.73

FATHMM_MKL

Benign

0.38

LIST_S2

Benign

0.42

M_CAP

Uncertain

0.12

MetaRNN

Benign

0.076

MetaSVM

Benign

-0.98

MutationAssessor

Benign

1.0

PrimateAI

Pathogenic

0.90

PROVEAN

Benign

-0.37

REVEL

Benign

0.023

Sift

Benign

0.085

Sift4G

Benign

0.25

Polyphen

0.0060

Vest4

0.16

MutPred

0.28

Loss of stability (P = 0.0092);

MVP

0.18

MPC

3.6

ClinPred

0.22

GERP RS

1.8

Varity_R

0.15

gMVP

0.27

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over