2-10043621-T-TGCC

Position:

• chr2-10043621-T-TGCC

Variant summary

Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP6 BS2

The NM_003597.5(KLF11):​c.-80_-78dupGCC variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.0086 (12 hom., cov: 0)
  • Exomes 𝑓: 0.011 (41 hom.)
• Consequence: KLF11 NM_003597.5 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:1 B:2
• Conservation: PhyloP100: 1.06

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]

ACMG classification

Verdict is Likely_benign. Variant got -5 ACMG points.

• BP6: Variant 2-10043621-T-TGCC is Benign according to our data. Variant chr2-10043621-T-TGCC is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 330619.We mark this variant Likely_benign, oryginal submissions are: {Likely_benign=1, Uncertain_significance=1, Benign=1}.
• BS2: High AC in GnomAd4 at 1250 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF11	NM_003597.5	c.-80_-78dupGCC		5_prime_UTR_variant	1/4	ENST00000305883.6	NP_003588.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883	c.-80_-78dupGCC		5_prime_UTR_variant	1/4	1	NM_003597.5	ENSP00000307023.1
KLF11	ENST00000401510.5	c.-10+566_-10+568dupGCC		intron_variant		3		ENSP00000386058.1

Frequencies

GnomAD3 genomes AF: 0.00864 AC: 1249 AN: 144568 Hom.: 12 Cov.: 0

Gnomad AFR AF: 0.00378

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00840

Gnomad ASJ AF: 0.00443

Gnomad EAS AF: 0.000834

Gnomad SAS AF: 0.00505

Gnomad FIN AF: 0.00662

Gnomad MID AF: 0.00333

Gnomad NFE AF: 0.0132

Gnomad OTH AF: 0.00699

GnomAD4 exome AF: 0.0114 AC: 8260 AN: 722846 Hom.: 41 Cov.: 2 AF XY: 0.0112 AC XY: 3874 AN XY: 344798

Gnomad4 AFR exome AF: 0.00203

Gnomad4 AMR exome AF: 0.00884

Gnomad4 ASJ exome AF: 0.00446

Gnomad4 EAS exome AF: 0.000881

Gnomad4 SAS exome AF: 0.00386

Gnomad4 FIN exome AF: 0.00876

Gnomad4 NFE exome AF: 0.0121

Gnomad4 OTH exome AF: 0.00868

GnomAD4 genome AF: 0.00864 AC: 1250 AN: 144684 Hom.: 12 Cov.: 0 AF XY: 0.00859 AC XY: 604 AN XY: 70350

Gnomad4 AFR AF: 0.00377

Gnomad4 AMR AF: 0.00838

Gnomad4 ASJ AF: 0.00443

Gnomad4 EAS AF: 0.000837

Gnomad4 SAS AF: 0.00505

Gnomad4 FIN AF: 0.00662

Gnomad4 NFE AF: 0.0132

Gnomad4 OTH AF: 0.00740

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:1 Benign:2

Revision: criteria provided, conflicting classifications

Submissions by phenotype

not provided Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 11, 2020	- -
Benign, criteria provided, single submitter	clinical testing	CeGaT Center for Human Genetics Tuebingen	Jun 01, 2023	KLF11: BS1, BS2 -

Maturity onset diabetes mellitus in young Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs372827624; hg19: chr2-10183748;