Variant 19-16325565-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6_ModerateBS1BS2

The NM_016270.4(KLF2):c.425G>A(p.Arg142His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000869 in 1,174,586 control chromosomes in the GnomAD database, including 6 homozygotes. 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 Benign (★).

Frequency

Genomes: 𝑓 0.0012 ( 1 hom., cov: 32)

Exomes 𝑓: 0.00083 ( 5 hom. )

Consequence

KLF2
NM_016270.4 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.953

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 -14 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0058060586).

BP6

Variant 19-16325565-G-A is Benign according to our data. Variant chr19-16325565-G-A is described in ClinVar as [Benign]. Clinvar id is 785616.Status of the report is criteria_provided_single_submitter, 1 stars.

BS1

Variant frequency is greater than expected in population eas. gnomad4 allele frequency = 0.00115 (172/149030) while in subpopulation EAS AF= 0.021 (107/5090). AF 95% confidence interval is 0.0178. There are 1 homozygotes in gnomad4. There are 90 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.

BS2

High AC in GnomAd4 at 172 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF2	NM_016270.4 link	c.425G>A	p.Arg142His	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.425G>A	p.Arg142His	missense_variant	2/3	1	NM_016270.4	ENSP00000248071.5		Q9Y5W3
KLF2	ENST00000592003.1 link	c.75+567G>A		intron_variant		3		ENSP00000465035.1		K7EJ60

Frequencies

GnomAD3 genomes

AF:

0.00118

AC:

175

AN:

148922

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000463

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000200

Gnomad ASJ

AF:

0.000293

Gnomad EAS

AF:

0.0213

Gnomad SAS

AF:

0.00458

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000254

Gnomad OTH

AF:

0.00194

GnomAD4 exome

AF:

0.000828

AC:

849

AN:

1025556

Hom.:

Cov.:

AF XY:

0.000807

AC XY:

391

AN XY:

484596

show subpopulations

Gnomad4 AFR exome

AF:

0.000195

Gnomad4 AMR exome

AF:

0.000157

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0202

Gnomad4 SAS exome

AF:

0.00340

Gnomad4 FIN exome

AF:

0.0000530

Gnomad4 NFE exome

AF:

0.000272

Gnomad4 OTH exome

AF:

0.00254

GnomAD4 genome

AF:

0.00115

AC:

172

AN:

149030

Hom.:

Cov.:

AF XY:

0.00124

AC XY:

AN XY:

72738

show subpopulations

Gnomad4 AFR

AF:

0.000462

Gnomad4 AMR

AF:

0.000200

Gnomad4 ASJ

AF:

0.000293

Gnomad4 EAS

AF:

0.0210

Gnomad4 SAS

AF:

0.00458

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000254

Gnomad4 OTH

AF:

0.00144

Alfa

AF:

0.0000530

Hom.:

Bravo

AF:

0.00145

ExAC

AF:

0.000813

AC:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Dec 17, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.69

BayesDel_noAF

Benign

-0.75

CADD

Benign

DANN

Uncertain

0.98

DEOGEN2

Benign

0.063

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.52

M_CAP

Benign

0.060

MetaRNN

Benign

0.0058

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.0

PrimateAI

Pathogenic

0.88

PROVEAN

Benign

0.15

REVEL

Benign

0.016

Sift

Benign

0.25

Sift4G

Benign

0.15

Polyphen

0.0010

Vest4

0.13

MutPred

0.36

Loss of MoRF binding (P = 0.0077);

MVP

0.33

MPC

1.8

ClinPred

0.11

GERP RS

-0.69

Varity_R

0.031

gMVP

0.20

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