rs15336

Variant names:

• chr19-16327202-C-A
• rs15336
• NM_016270.4:c.*171C>A

Your query was ambiguous. Multiple possible variants found:

• chr19-16327202-C-A
• chr19-16327202-C-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_016270.4(KLF2):​c.*171C>A variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.15 in 602,548 control chromosomes in the GnomAD database, including 7,747 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.15 (1861 hom., cov: 32)
  • Exomes 𝑓: 0.15 (5886 hom.)
• Consequence: KLF2 NM_016270.4 3_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.53
• Publications: 7 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.63).
• BP6: Variant 19-16327202-C-A is Benign according to our data. Variant chr19-16327202-C-A is described in ClinVar as Benign. ClinVar VariationId is 1182815.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.17 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF2	NM_016270.4	c.*171C>A		3_prime_UTR_variant	Exon 3 of 3	ENST00000248071.6	NP_057354.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF2	ENST00000248071.6	c.*171C>A		3_prime_UTR_variant	Exon 3 of 3	1	NM_016270.4	ENSP00000248071.5
KLF2	ENST00000592003.1	c.*185C>A		3_prime_UTR_variant	Exon 2 of 2	3		ENSP00000465035.1

Frequencies

GnomAD3 genomes AF: 0.151 AC: 22900 AN: 152024 Hom.: 1861 Cov.: 32

Gnomad AFR AF: 0.133

Gnomad AMI AF: 0.183

Gnomad AMR AF: 0.128

Gnomad ASJ AF: 0.150

Gnomad EAS AF: 0.00694

Gnomad SAS AF: 0.0621

Gnomad FIN AF: 0.220

Gnomad MID AF: 0.123

Gnomad NFE AF: 0.173

Gnomad OTH AF: 0.156

GnomAD4 exome AF: 0.150 AC: 67549 AN: 450412 Hom.: 5886 Cov.: 6 AF XY: 0.146 AC XY: 34243 AN XY: 234954

African (AFR) AF: 0.137 AC: 1530 AN: 11176

American (AMR) AF: 0.110 AC: 1622 AN: 14780

Ashkenazi Jewish (ASJ) AF: 0.155 AC: 1897 AN: 12242

East Asian (EAS) AF: 0.0113 AC: 325 AN: 28656

South Asian (SAS) AF: 0.0588 AC: 2361 AN: 40142

European-Finnish (FIN) AF: 0.199 AC: 5759 AN: 28950

Middle Eastern (MID) AF: 0.150 AC: 279 AN: 1860

European-Non Finnish (NFE) AF: 0.174 AC: 50035 AN: 287746

Other (OTH) AF: 0.150 AC: 3741 AN: 24860

GnomAD4 genome AF: 0.151 AC: 22905 AN: 152136 Hom.: 1861 Cov.: 32 AF XY: 0.150 AC XY: 11153 AN XY: 74348

African (AFR) AF: 0.133 AC: 5505 AN: 41508

American (AMR) AF: 0.128 AC: 1953 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.150 AC: 521 AN: 3468

East Asian (EAS) AF: 0.00696 AC: 36 AN: 5174

South Asian (SAS) AF: 0.0623 AC: 301 AN: 4828

European-Finnish (FIN) AF: 0.220 AC: 2332 AN: 10582

Middle Eastern (MID) AF: 0.129 AC: 38 AN: 294

European-Non Finnish (NFE) AF: 0.173 AC: 11727 AN: 67980

Other (OTH) AF: 0.155 AC: 326 AN: 2110

Alfa AF: 0.140 Hom.: 759

Bravo AF: 0.144

Asia WGS AF: 0.0440 AC: 154 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

May 13, 2021

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.87
PhyloP100		1.5
Mutation Taster		=100/0	polymorphism (auto)

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: rs15336; hg19: chr19-16438013;