rs755357629

Variant names:

• chr19-16325403-C-G
• rs755357629
• NM_016270.4:c.263C>G

Your query was ambiguous. Multiple possible variants found:

• chr19-16325403-C-G
• chr19-16325403-C-A

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Moderate BS2

The NM_016270.4(KLF2):​c.263C>G​(p.Ala88Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000604 in 1,424,856 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.000053 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000061 (0 hom.)
• Consequence: KLF2 NM_016270.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.33
• Publications: 0 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: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.13834009).
• BS2: High AC in GnomAd4 at 8 AD gene.

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.263C>G	p.Ala88Gly	missense	Exon 2 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.263C>G	p.Ala88Gly	missense	Exon 2 of 3	ENSP00000248071.5	Q9Y5W3
	KLF2	ENST00000592003.1	TSL:3	c.75+405C>G		intron	N/A	ENSP00000465035.1	K7EJ60

Frequencies

GnomAD3 genomes AF: 0.0000528 AC: 8 AN: 151636 Hom.: 0 Cov.: 33

Gnomad AFR AF: 0.0000242

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000612 AC: 3 AN: 49004 AF XY: 0.0000671

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000126

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000613 AC: 78 AN: 1273220 Hom.: 0 Cov.: 34 AF XY: 0.0000589 AC XY: 37 AN XY: 627722

African (AFR) AF: 0.00 AC: 0 AN: 24942

American (AMR) AF: 0.00 AC: 0 AN: 15502

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18862

East Asian (EAS) AF: 0.00 AC: 0 AN: 28990

South Asian (SAS) AF: 0.00 AC: 0 AN: 63318

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 31952

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4026

European-Non Finnish (NFE) AF: 0.0000755 AC: 78 AN: 1033256

Other (OTH) AF: 0.00 AC: 0 AN: 52372

GnomAD4 genome AF: 0.0000528 AC: 8 AN: 151636 Hom.: 0 Cov.: 33 AF XY: 0.0000270 AC XY: 2 AN XY: 74048

African (AFR) AF: 0.0000242 AC: 1 AN: 41356

American (AMR) AF: 0.00 AC: 0 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3468

East Asian (EAS) AF: 0.00 AC: 0 AN: 5130

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10460

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.000103 AC: 7 AN: 67850

Other (OTH) AF: 0.00 AC: 0 AN: 2086

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000529

ExAC AF: 0.0000202 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.17
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.69
CADD	Benign	19
DANN	Benign	0.95
DEOGEN2	Benign	0.059	T
Eigen	Benign	-0.46
Eigen_PC	Benign	-0.55
FATHMM_MKL	Benign	0.50	N
LIST_S2	Benign	0.41	T
M_CAP	Pathogenic	0.29	D
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.82	T
MutationAssessor	Benign	0.69	N
PhyloP100		1.3
PrimateAI	Pathogenic	0.88	D
PROVEAN	Benign	-0.070	N
REVEL	Benign	0.065
Sift	Benign	0.52	T
Sift4G	Benign	0.32	T
Polyphen		0.96	D
Vest4		0.13
MutPred		0.29		Gain of relative solvent accessibility (P = 0.0023)
MVP		0.63
MPC		1.9
ClinPred		0.11	T
GERP RS		1.2
Varity_R		0.067
gMVP		0.082
Mutation Taster		=96/4	polymorphism

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

Other links and lift over

dbSNP: rs755357629; hg19: chr19-16436214;