2-10043621-TGCC-T

Position:

• chr2-10043621-TGCC-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_003597.5(KLF11):​c.-80_-78del variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.283 in 863,710 control chromosomes in the GnomAD database, including 35,108 homozygotes. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.31 (7211 hom., cov: 0)
  • Exomes 𝑓: 0.28 (27897 hom.)
• Consequence: KLF11 NM_003597.5 5_prime_UTR
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts 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 Benign. Variant got -16 ACMG points.

• BP6: Variant 2-10043621-TGCC-T is Benign according to our data. Variant chr2-10043621-TGCC-T is described in ClinVar as [Benign]. Clinvar id is 330618.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.391 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
KLF11	NM_003597.5	c.-80_-78del		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	ENST00000305883.6	c.-80_-78del		5_prime_UTR_variant	1/4	1	NM_003597.5	ENSP00000307023	A2
KLF11	ENST00000401510.5	c.-10+566_-10+568del		intron_variant		3		ENSP00000386058

Frequencies

GnomAD3 genomes AF: 0.311 AC: 44979 AN: 144434 Hom.: 7194 Cov.: 0

Gnomad AFR AF: 0.396

Gnomad AMI AF: 0.439

Gnomad AMR AF: 0.251

Gnomad ASJ AF: 0.339

Gnomad EAS AF: 0.172

Gnomad SAS AF: 0.308

Gnomad FIN AF: 0.210

Gnomad MID AF: 0.453

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.318

GnomAD4 exome AF: 0.277 AC: 199537 AN: 719160 Hom.: 27897 AF XY: 0.279 AC XY: 95555 AN XY: 342958

Gnomad4 AFR exome AF: 0.398

Gnomad4 AMR exome AF: 0.244

Gnomad4 ASJ exome AF: 0.341

Gnomad4 EAS exome AF: 0.163

Gnomad4 SAS exome AF: 0.329

Gnomad4 FIN exome AF: 0.251

Gnomad4 NFE exome AF: 0.273

Gnomad4 OTH exome AF: 0.291

GnomAD4 genome AF: 0.312 AC: 45035 AN: 144550 Hom.: 7211 Cov.: 0 AF XY: 0.304 AC XY: 21388 AN XY: 70286

Gnomad4 AFR AF: 0.396

Gnomad4 AMR AF: 0.251

Gnomad4 ASJ AF: 0.339

Gnomad4 EAS AF: 0.172

Gnomad4 SAS AF: 0.307

Gnomad4 FIN AF: 0.210

Gnomad4 NFE AF: 0.292

Gnomad4 OTH AF: 0.321

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Maturity onset diabetes mellitus in young Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Aug 10, 2019

- -

Computational scores

Source: dbNSFP v4.3

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: rs372827624; hg19: chr2-10183748;