rs12462380

Variant names:

• chr19-16326237-A-G
• rs12462380
• NM_016270.4:c.892+205A>G

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+205A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. 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 0.49 (15703 hom., cov: 20)
• Consequence: KLF2 NM_016270.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.912
• Publications: 9 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 = 0.543 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF2	NM_016270.4	c.892+205A>G		intron_variant	Intron 2 of 2	ENST00000248071.6	NP_057354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6	c.892+205A>G		intron_variant	Intron 2 of 2	1	NM_016270.4	ENSP00000248071.5
KLF2	ENST00000592003.1	c.76-619A>G		intron_variant	Intron 1 of 1	3		ENSP00000465035.1

Frequencies

GnomAD3 genomes AF: 0.488 AC: 66696 AN: 136626 Hom.: 15671 Cov.: 20

Gnomad AFR AF: 0.549

Gnomad AMI AF: 0.505

Gnomad AMR AF: 0.549

Gnomad ASJ AF: 0.394

Gnomad EAS AF: 0.457

Gnomad SAS AF: 0.545

Gnomad FIN AF: 0.520

Gnomad MID AF: 0.552

Gnomad NFE AF: 0.439

Gnomad OTH AF: 0.466

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

GnomAD4 genome AF: 0.488 AC: 66775 AN: 136714 Hom.: 15703 Cov.: 20 AF XY: 0.495 AC XY: 32559 AN XY: 65786

African (AFR) AF: 0.550 AC: 19988 AN: 36350

American (AMR) AF: 0.549 AC: 7489 AN: 13638

Ashkenazi Jewish (ASJ) AF: 0.394 AC: 1290 AN: 3270

East Asian (EAS) AF: 0.457 AC: 2010 AN: 4394

South Asian (SAS) AF: 0.544 AC: 2289 AN: 4206

European-Finnish (FIN) AF: 0.520 AC: 4430 AN: 8518

Middle Eastern (MID) AF: 0.553 AC: 147 AN: 266

European-Non Finnish (NFE) AF: 0.439 AC: 27863 AN: 63408

Other (OTH) AF: 0.464 AC: 856 AN: 1846

Alfa AF: 0.440 Hom.: 19118

Bravo AF: 0.471

Asia WGS AF: 0.476 AC: 1655 AN: 3474

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	5.6
DANN	Benign	0.45
PhyloP100		-0.91
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs12462380; hg19: chr19-16437048;