2-10047747-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_003597.5(KLF11):c.410A>G(p.Asp137Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000563 in 1,613,718 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0030 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00031 ( 2 hom. )

Consequence

KLF11
NM_003597.5 missense

Scores

Clinical Significance

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

Conservation

PhyloP100: 1.30

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0035626292).

BP6

Variant 2-10047747-A-G is Benign according to our data. Variant chr2-10047747-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 129430.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-10047747-A-G is described in Lovd as [Likely_benign].

BS2

High AC in GnomAd4 at 456 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
KLF11	NM_003597.5 link	c.410A>G	p.Asp137Gly	missense_variant	Exon 3 of 4	ENST00000305883.6	NP_003588.1	O14901-1Q53QU8
KLF11	NM_001177716.2 link	c.359A>G	p.Asp120Gly	missense_variant	Exon 3 of 4		NP_001171187.1	O14901-2B7ZAX4
KLF11	NM_001177718.2 link	c.359A>G	p.Asp120Gly	missense_variant	Exon 3 of 4		NP_001171189.1	O14901-2
KLF11	XM_047446025.1 link	c.359A>G	p.Asp120Gly	missense_variant	Exon 3 of 4		XP_047301981.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
KLF11	ENST00000305883.6 link	c.410A>G	p.Asp137Gly	missense_variant	Exon 3 of 4	1	NM_003597.5	ENSP00000307023.1		O14901-1

Frequencies

GnomAD3 genomes

AF:

0.00298

AC:

454

AN:

152110

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0107

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.000753

AC:

189

AN:

251138

Hom.:

AF XY:

0.000552

AC XY:

AN XY:

135774

show subpopulations

Gnomad AFR exome

AF:

0.0102

Gnomad AMR exome

AF:

0.000521

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.000326

GnomAD4 exome

AF:

0.000310

AC:

453

AN:

1461488

Hom.:

Cov.:

AF XY:

0.000293

AC XY:

213

AN XY:

727080

show subpopulations

Gnomad4 AFR exome

AF:

0.0102

Gnomad4 AMR exome

AF:

0.000581

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000414

Gnomad4 OTH exome

AF:

0.000629

GnomAD4 genome

AF:

0.00300

AC:

456

AN:

152230

Hom.:

Cov.:

AF XY:

0.00324

AC XY:

241

AN XY:

74436

show subpopulations

Gnomad4 AFR

AF:

0.0107

Gnomad4 AMR

AF:

0.000458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.000367

Hom.:

Bravo

AF:

0.00316

ESP6500AA

AF:

0.00999

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000939

AC:

114

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Jan 23, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jun 22, 2021

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Sep 05, 2013

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Monogenic diabetes

Benign:1

Jun 26, 2017

Personalized Diabetes Medicine Program, University of Maryland School of Medicine

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: research

ACMG Criteria:BP4 (9 predictors), BS2 (24 cases and 17 controls in type2diabetesgenetics.org), BS1 (1.21% 1000G African) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.18

BayesDel_addAF

Benign

-0.45

BayesDel_noAF

Benign

-0.41

CADD

Benign

9.8

DANN

Benign

0.41

DEOGEN2

Benign

0.055

T;T;.;.;T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.31

LIST_S2

Benign

0.51

T;T;T;T;T;.

MetaRNN

Benign

0.0036

T;T;T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.34

.;N;.;.;.;.

PrimateAI

Benign

0.33

PROVEAN

Benign

0.13

N;N;N;N;N;N

REVEL

Benign

0.055

Sift

Benign

0.61

T;T;T;T;T;T

Sift4G

Benign

0.62

T;T;T;T;T;T

Polyphen

0.0090

.;B;.;.;.;.

Vest4

0.13, 0.12, 0.12

MVP

0.48

MPC

0.023

ClinPred

0.0013

GERP RS

3.1

Varity_R

0.041

gMVP

0.16

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.040

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over