chr2-10046292-A-G

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_003597.5(KLF11):c.185A>G(p.Gln62Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.108 in 1,614,130 control chromosomes in the GnomAD database, including 10,225 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.088 ( 712 hom., cov: 33)

Exomes 𝑓: 0.11 ( 9513 hom. )

Consequence

KLF11
NM_003597.5 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts P:1B:5

Conservation

PhyloP100: 2.09

Publications

37 publications found

Variant links:

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]

KLF11 Gene-Disease associations (from GenCC):

maturity-onset diabetes of the young type 7
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
maturity-onset diabetes of the young
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
monogenic diabetes
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

KLF11 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0014551878).

BP6

Variant 2-10046292-A-G is Benign according to our data. Variant chr2-10046292-A-G is described in ClinVar as Benign/Likely_benign. ClinVar VariationId is 129431.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.117 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5 link	c.185A>G	p.Gln62Arg	missense_variant	Exon 2 of 4	ENST00000305883.6	NP_003588.1	O14901-1Q53QU8
KLF11	NM_001177716.2 link	c.134A>G	p.Gln45Arg	missense_variant	Exon 2 of 4		NP_001171187.1	O14901-2B7ZAX4
KLF11	NM_001177718.2 link	c.134A>G	p.Gln45Arg	missense_variant	Exon 2 of 4		NP_001171189.1	O14901-2
KLF11	XM_047446025.1 link	c.134A>G	p.Gln45Arg	missense_variant	Exon 2 of 4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6 link	c.185A>G	p.Gln62Arg	missense_variant	Exon 2 of 4	1	NM_003597.5	ENSP00000307023.1		O14901-1

Frequencies

GnomAD3 genomes

AF:

0.0877

AC:

13342

AN:

152154

Hom.:

712

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0466

Gnomad AMI

AF:

0.228

Gnomad AMR

AF:

0.0888

Gnomad ASJ

AF:

0.137

Gnomad EAS

AF:

0.00115

Gnomad SAS

AF:

0.0628

Gnomad FIN

AF:

0.0684

Gnomad MID

AF:

0.108

Gnomad NFE

AF:

0.119

Gnomad OTH

AF:

0.0999

GnomAD2 exomes

AF:

0.0926

AC:

23274

AN:

251402

AF XY:

0.0954

show subpopulations

Gnomad AFR exome

AF:

0.0459

Gnomad AMR exome

AF:

0.0728

Gnomad ASJ exome

AF:

0.145

Gnomad EAS exome

AF:

0.000653

Gnomad FIN exome

AF:

0.0773

Gnomad NFE exome

AF:

0.123

Gnomad OTH exome

AF:

0.109

GnomAD4 exome

AF:

0.110

AC:

160944

AN:

1461858

Hom.:

9513

Cov.:

AF XY:

0.109

AC XY:

79569

AN XY:

727230

show subpopulations

African (AFR)

AF:

0.0445

AC:

1490

AN:

33480

American (AMR)

AF:

0.0737

AC:

3295

AN:

44722

Ashkenazi Jewish (ASJ)

AF:

0.144

AC:

3753

AN:

26136

East Asian (EAS)

AF:

0.000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0731

AC:

6309

AN:

86258

European-Finnish (FIN)

AF:

0.0785

AC:

4195

AN:

53420

Middle Eastern (MID)

AF:

0.142

AC:

819

AN:

5768

European-Non Finnish (NFE)

AF:

0.121

AC:

134904

AN:

1111980

Other (OTH)

AF:

0.102

AC:

6169

AN:

60394

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.487

Heterozygous variant carriers

8876

17753

26629

35506

44382

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

4798

9596

14394

19192

23990

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0876

AC:

13345

AN:

152272

Hom.:

712

Cov.:

AF XY:

0.0849

AC XY:

6321

AN XY:

74474

show subpopulations

African (AFR)

AF:

0.0466

AC:

1937

AN:

41554

American (AMR)

AF:

0.0887

AC:

1358

AN:

15302

Ashkenazi Jewish (ASJ)

AF:

0.137

AC:

477

AN:

3470

East Asian (EAS)

AF:

0.00116

AC:

AN:

5186

South Asian (SAS)

AF:

0.0624

AC:

301

AN:

4820

European-Finnish (FIN)

AF:

0.0684

AC:

726

AN:

10614

Middle Eastern (MID)

AF:

0.105

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.119

AC:

8091

AN:

68006

Other (OTH)

AF:

0.0993

AC:

210

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.505

Heterozygous variant carriers

630

1261

1891

2522

3152

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

154

308

462

616

770

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.113

Hom.:

1934

Bravo

AF:

0.0885

TwinsUK

AF:

0.117

AC:

433

ALSPAC

AF:

0.116

AC:

447

ESP6500AA

AF:

0.0429

AC:

189

ESP6500EA

AF:

0.121

AC:

1044

ExAC

AF:

0.0926

AC:

11249

Asia WGS

AF:

0.0340

AC:

119

AN:

3478

EpiCase

AF:

0.131

EpiControl

AF:

0.134

ClinVar

Significance: Benign/Likely benign

Submissions summary: Pathogenic:1Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:2

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Likely benign based on allele frequency in 1000 Genomes Project or ESP global frequency and its presence in a patient with a rare or unrelated disease phenotype. NOT Sanger confirmed. -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 15774581) -

Feb 01, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Type 2 diabetes mellitus

Pathogenic:1

Clinical Genomics, Uppaluri K&H Personalized Medicine Clinic

Significance:Likely risk allele

Review Status:flagged submission

Collection Method:research

KLF11 gene mutations are associated with MODY, however it needs further validation via clinical studies. This particular variant (rs35927125) of KLF11 gene can trigger Type II Diabetes Mellitus. However, more studies are required in different ethnic groups to ascertain its significance. -

Maturity-onset diabetes of the young type 7

Benign:1

Apr 27, 2017

Illumina Laboratory Services, Illumina

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.27

BayesDel_addAF

Benign

-0.56

BayesDel_noAF

Benign

-0.48

CADD

Benign

(source)

DANN

Benign

0.97

DEOGEN2

Benign

0.11

T;T;.;.;T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.48

FATHMM_MKL

Uncertain

0.78

LIST_S2

Benign

0.44

T;T;T;T;T;.

MetaRNN

Benign

0.0015

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Uncertain

2.2

.;M;.;.;.;.

PhyloP100

2.1

PrimateAI

Benign

0.38

PROVEAN

Benign

-1.7

N;N;N;N;N;N

REVEL

Benign

0.069

Sift

Benign

0.23

T;D;T;T;T;T

Sift4G

Benign

0.11

T;T;T;T;T;T

Polyphen

0.0030

.;B;.;.;.;.

Vest4

0.077, 0.097, 0.091

MPC

0.022

ClinPred

0.0058

GERP RS

-0.46

Varity_R

0.12

gMVP

0.11

Mutation Taster

=98/2

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over