Variant 19-16324988-G-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_016270.4(KLF2):c.65G>C(p.Gly22Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 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: 0.0 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

KLF2
NM_016270.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.52

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 Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.036241025).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF2	NM_016270.4 linkuse as main transcript	c.65G>C	p.Gly22Ala	missense_variant	1/3	ENST00000248071.6	NP_057354.1	Q9Y5W3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6 linkuse as main transcript	c.65G>C	p.Gly22Ala	missense_variant	1/3	1	NM_016270.4	ENSP00000248071.5		Q9Y5W3
KLF2	ENST00000592003.1 linkuse as main transcript	c.65G>C	p.Gly22Ala	missense_variant	1/2	3		ENSP00000465035.1		K7EJ60

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Data not reliable, filtered out with message: AC0

AF:

0.00

AC:

AN:

1446638

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

719268

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:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

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

Oct 05, 2021

The c.65G>C (p.G22A) alteration is located in exon 1 (coding exon 1) of the KLF2 gene. This alteration results from a G to C substitution at nucleotide position 65, causing the glycine (G) at amino acid position 22 to be replaced by an alanine (A). 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

Benign

0.19

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.67

CADD

Benign

DANN

Benign

0.42

DEOGEN2

Benign

0.057

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.97

FATHMM_MKL

Benign

0.031

LIST_S2

Benign

0.67

T;T

M_CAP

Benign

0.072

MetaRNN

Benign

0.036

T;T

MetaSVM

Benign

-0.92

MutationAssessor

Benign

0.90

L;.

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.27

N;.

REVEL

Benign

0.038

Sift

Benign

0.92

T;.

Sift4G

Benign

0.64

T;D

Polyphen

0.015

B;.

Vest4

0.073

MutPred

0.23

Gain of helix (P = 0.0325);Gain of helix (P = 0.0325);

MVP

0.31

MPC

2.8

ClinPred

0.072

GERP RS

0.12

Varity_R

0.081

gMVP

0.11

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