19-16326424-A-T

Variant names:

• chr19-16326424-A-T
• rs7258799
• NM_016270.4:c.892+392A>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_016270.4(KLF2):​c.892+392A>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.123 in 151,894 control chromosomes in the GnomAD database, including 1,258 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 0.12 (1258 hom., cov: 31)
• Consequence: KLF2 NM_016270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.67
• Publications: 3 publications found

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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 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.892+392A>T		intron	N/A	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.892+392A>T		intron	N/A	ENSP00000248071.5	Q9Y5W3
	KLF2	ENST00000592003.1	TSL:3	c.76-432A>T		intron	N/A	ENSP00000465035.1	K7EJ60

Frequencies

GnomAD3 genomes AF: 0.123 AC: 18614 AN: 151776 Hom.: 1256 Cov.: 31

Gnomad AFR AF: 0.151

Gnomad AMI AF: 0.0529

Gnomad AMR AF: 0.116

Gnomad ASJ AF: 0.221

Gnomad EAS AF: 0.0143

Gnomad SAS AF: 0.0949

Gnomad FIN AF: 0.0662

Gnomad MID AF: 0.193

Gnomad NFE AF: 0.121

Gnomad OTH AF: 0.144

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.123 AC: 18620 AN: 151894 Hom.: 1258 Cov.: 31 AF XY: 0.119 AC XY: 8847 AN XY: 74234

African (AFR) AF: 0.151 AC: 6236 AN: 41402

American (AMR) AF: 0.116 AC: 1762 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 765 AN: 3466

East Asian (EAS) AF: 0.0144 AC: 74 AN: 5148

South Asian (SAS) AF: 0.0960 AC: 462 AN: 4810

European-Finnish (FIN) AF: 0.0662 AC: 701 AN: 10590

Middle Eastern (MID) AF: 0.177 AC: 52 AN: 294

European-Non Finnish (NFE) AF: 0.121 AC: 8221 AN: 67920

Other (OTH) AF: 0.142 AC: 299 AN: 2104

Alfa AF: 0.0664 Hom.: 68

Bravo AF: 0.127

Asia WGS AF: 0.0670 AC: 233 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.35
DANN	Benign	0.73
PhyloP100		-1.7
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.080		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs7258799; hg19: chr19-16437235;