dbSNP rs8810: KLF2:c.*473A>T (chr19-16327504-A-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_ModerateBA1

The NM_016270.4(KLF2):c.*473A>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.242 in 151,138 control chromosomes in the GnomAD database, including 5,128 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.24 ( 5106 hom., cov: 31)

Exomes 𝑓: 0.20 ( 22 hom. )

Consequence

KLF2
NM_016270.4 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 3.21

Publications

4 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:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_016270.4, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.31).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.376 is higher than 0.05.

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.*473A>T		3_prime_UTR	Exon 3 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.*473A>T		3_prime_UTR	Exon 3 of 3	ENSP00000248071.5	Q9Y5W3
	KLF2	ENST00000592003.1	TSL:3	c.*487A>T		downstream_gene	N/A	ENSP00000465035.1	K7EJ60

Frequencies

GnomAD3 genomes

AF:

0.243

AC:

36462

AN:

150336

Hom.:

5108

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0922

Gnomad AMI

AF:

0.290

Gnomad AMR

AF:

0.317

Gnomad ASJ

AF:

0.286

Gnomad EAS

AF:

0.254

Gnomad SAS

AF:

0.393

Gnomad FIN

AF:

0.243

Gnomad MID

AF:

0.328

Gnomad NFE

AF:

0.302

Gnomad OTH

AF:

0.264

GnomAD4 exome

AF:

0.204

AC:

141

AN:

690

Hom.:

Cov.:

AF XY:

0.237

AC XY:

103

AN XY:

434

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

American (AMR)

AF:

0.147

AC:

AN:

Ashkenazi Jewish (ASJ)

AF:

0.300

AC:

AN:

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.284

AC:

AN:

236

European-Finnish (FIN)

AF:

0.214

AC:

AN:

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.174

AC:

AN:

322

Other (OTH)

AF:

0.154

AC:

AN:

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.516

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

AF:

0.242

AC:

36462

AN:

150448

Hom.:

5106

Cov.:

AF XY:

0.244

AC XY:

17926

AN XY:

73464

show subpopulations

African (AFR)

AF:

0.0919

AC:

3773

AN:

41036

American (AMR)

AF:

0.317

AC:

4806

AN:

15152

Ashkenazi Jewish (ASJ)

AF:

0.286

AC:

989

AN:

3460

East Asian (EAS)

AF:

0.255

AC:

1313

AN:

5156

South Asian (SAS)

AF:

0.391

AC:

1869

AN:

4778

European-Finnish (FIN)

AF:

0.243

AC:

2496

AN:

10252

Middle Eastern (MID)

AF:

0.336

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.302

AC:

20309

AN:

67338

Other (OTH)

AF:

0.263

AC:

551

AN:

2094

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1306

2612

3918

5224

6530

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

404

808

1212

1616

2020

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.259

Hom.:

538

Bravo

AF:

0.238

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.31

CADD

Benign

(source)

DANN

Benign

0.90

PhyloP100

3.2

Mutation Taster

=100/0

polymorphism (auto)

(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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over