2-10043421-A-G

Position:

• chr2-10043421-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BS1 BS2

The ENST00000401510.5(KLF11):​c.-10+350A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0198 in 90,554 control chromosomes in the GnomAD database, including 26 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.020 (25 hom., cov: 26)
  • Exomes 𝑓: 0.063 (1 hom.)
• Consequence: KLF11 ENST00000401510.5 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.16

Genes affected

KLF11 (HGNC:11811): (KLF transcription factor 11) The protein encoded by this gene is a zinc finger transcription factor that binds to SP1-like sequences in epsilon- and gamma-globin gene promoters. This binding inhibits cell growth and causes apoptosis. Defects in this gene are a cause of maturity-onset diabetes of the young type 7 (MODY7). Three transcript variants encoding two different isoforms have been found for this gene. [provided by RefSeq, Apr 2010]

(HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.22).
• BP6: Variant 2-10043421-A-G is Benign according to our data. Variant chr2-10043421-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 1316851.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0197 (1786/90506) while in subpopulation NFE AF= 0.0253 (1131/44684). AF 95% confidence interval is 0.0241. There are 25 homozygotes in gnomad4. There are 821 alleles in male gnomad4 subpopulation. Median coverage is 26. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 1786 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
		n.10043421A>G		intergenic_region
KLF11-DT	NR_135558.1	n.-20T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000401510.5	c.-10+350A>G		intron_variant		3		ENSP00000386058.1

Frequencies

GnomAD3 genomes AF: 0.0198 AC: 1791 AN: 90456 Hom.: 25 Cov.: 26

Gnomad AFR AF: 0.00592

Gnomad AMI AF: 0.175

Gnomad AMR AF: 0.0230

Gnomad ASJ AF: 0.0157

Gnomad EAS AF: 0.00140

Gnomad SAS AF: 0.00838

Gnomad FIN AF: 0.0211

Gnomad MID AF: 0.0814

Gnomad NFE AF: 0.0253

Gnomad OTH AF: 0.0278

GnomAD4 exome AF: 0.0625 AC: 3 AN: 48 Hom.: 1 AF XY: 0.0769 AC XY: 2 AN XY: 26

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 NFE exome AF: 0.0789

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0197 AC: 1786 AN: 90506 Hom.: 25 Cov.: 26 AF XY: 0.0188 AC XY: 821 AN XY: 43750

Gnomad4 AFR AF: 0.00591

Gnomad4 AMR AF: 0.0228

Gnomad4 ASJ AF: 0.0157

Gnomad4 EAS AF: 0.00140

Gnomad4 SAS AF: 0.00838

Gnomad4 FIN AF: 0.0211

Gnomad4 NFE AF: 0.0253

Gnomad4 OTH AF: 0.0277

Bravo AF: 0.0128

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 25, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.22
CADD	Benign	19
DANN	Benign	0.95

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs748383431; hg19: chr2-10183548;