chr19-16327202-C-A

Position:

• chr19-16327202-C-A

Variant summary

Our verdict is Benign. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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 id 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/exons	MANE	UniProt
KLF2	NM_016270.4	c.*171C>A		3_prime_UTR_variant	3/3	ENST00000248071.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
KLF2	ENST00000248071.6	c.*171C>A		3_prime_UTR_variant	3/3	1	NM_016270.4	P1
KLF2	ENST00000592003.1	c.*185C>A		3_prime_UTR_variant	2/2	3

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

Gnomad4 AFR exome AF: 0.137

Gnomad4 AMR exome AF: 0.110

Gnomad4 ASJ exome AF: 0.155

Gnomad4 EAS exome AF: 0.0113

Gnomad4 SAS exome AF: 0.0588

Gnomad4 FIN exome AF: 0.199

Gnomad4 NFE exome AF: 0.174

Gnomad4 OTH exome AF: 0.150

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

Gnomad4 AFR AF: 0.133

Gnomad4 AMR AF: 0.128

Gnomad4 ASJ AF: 0.150

Gnomad4 EAS AF: 0.00696

Gnomad4 SAS AF: 0.0623

Gnomad4 FIN AF: 0.220

Gnomad4 NFE AF: 0.173

Gnomad4 OTH AF: 0.155

Alfa AF: 0.137 Hom.: 621

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

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	May 13, 2021	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.63
CADD	Benign	17
DANN	Benign	0.87

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

Publications

LitVar

Other links and lift over

dbSNP: rs15336; hg19: chr19-16438013;